A Prospective, Multi-center, Single Arm Post-market Clinical Follow-up (PMCF) Study to Evaluate the Safety and Performance of ENTACT™ (Next Generation) Resorbable Septal Staple System for Septoplasty
Conditions: Septoplasty
Sponsor: Smith & Nephew, Inc.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 1 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Sponsor Name and Address: 
Smith + Nephew, Inc. 
7135 Goodlett Farms Parkway, 
 Cordova, TN 38016 
 
 
 
Investigational Product(s) 
ENTACT™ Septal Stapler (Next Generation) 
 
 
Protocol Author(s): 
Esvanhnelly Podany, MPH  
Clinical Study Manager 
Smith + Nephew, Inc 
 
Stephan Mangin 
Global Clinical Strategy Lead 
Smith + Nephew, Inc 
 
Michelle Foster, BSc 
Senior Biostatistician 
Smith + Nephew, Inc 
 
Niraj Parikh 
Director of Health Economics 
Smith + Nephew, Inc 
 
 
 
 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 2 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
SIGNATURES
PRINCIPAL INVESTIGATOR SIGNATURE PAGE
This page will be returned to Smith + Nephew, Inc. and a copy retained at the investigational 
site.
I have read the attached protocol entitled “A prospective, multi-center, single arm PMCF study 
to evaluate the safety and performance of ENTACT™(Next Generation) resorbable septal
staple system for septoplasty”, version 2.0, dated 27Aug2020, and agree to abide by all 
provisions set forth herein.
I agree to comply with the Investigator’s Obligations stipulated in Section 21.5 of the protocol, 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the described clinical investigation without the prior 
written consent of Smith + Nephew, Inc.
Name, Address, 
Professional Position
Signature
Date Signed
(DD/MMM/YYYY)

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 3 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
COORDINATING INVESTIGATOR APPROVAL 
I have read the attached protocol entitled “A prospective, multi-center, single arm PMCF study 
to evaluate the safety and performance of ENTACT™(Next Generation) resorbable septal
staple system for septoplasty”, version 2.0, dated 27Aug2020 , and agree to abide by all 
provisions set forth therein. 
Name, Address, 
Professional Position
Signature
Date Signed
(DD/MMM/YYYY)

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 4 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
SPONSOR APPROVAL
Job title
DocuSign Stamp
Head of Global Clinical 
Operations
Rachael Winter, Senior 
Director Global Clinical 
Operations
Head of Global Clinical 
Strategy
Stephan Mangin, 
Clinical Strategy 
Director
Head of Global Data 
Analytics
Alan Rossington, 
Director Biostatistics 
and Data Management
Medical Affairs 
Representative
Luca Orlandini, Vice 
President Medical 
Affairs
Regulatory 
Representative 
Piedad Pena, Manager 
Regulatory Affairs, 
Coblation, ENT

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 5 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
SYNOPSIS
Title of Study:
A prospective, multi-center, single arm PMCF study to evaluate the
safety and performance of ENTACT™(Next Generation) resorbable 
septal staple system for septoplasty
Study Design:
A prospective, multi-center, single arm case series
Study Type:
Observational, non- interventional,  post-market clinical follow-up 
(PMCF) study 
Study Product: 
ENTACT™Septal Stapler
Reference #
Description
Contains
601-00100*
ENTACT SEPTAL STAPLER, 
3-PACK 
3 ENTACT
Staplers
* The ENTACT (Next Generation) Septal Stapler will launch with the same reference # number
as the previous generation. Previous generation products already at customer sites will remain 
for consumption at launch in the US but are not part of the study. 
Septoplasty- The ENTACT Septal Stapler delivers implantable septal 
staples which are intended to connect internal tissues to aid healing 
and for approximation of soft tissue during nasal septal surgery.
Study Purpose:
To provide evidence to satisfy the Post-Market Clinical Follow-up 
(PMCF) requirements of CE Marking to market this device in Europe 
(data may be used to support registrations in other countries as well).
Primary Objective:
The primary objective of this study is to demonstrate clinical success 
of the ENTACT (Next Generation) resorbable septal staple system by 
examining the patient’s nasal cavity at the 21 day follow-up visit.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 6 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Secondary Objective(s): The secondary objectives are to generate performance and health 
economics data to support the use of ENTACT (Next Generation) 
resorbable septal staple. 
Safety Objective(s): 
Assess safety with reported complications, adverse events, adverse 
device effects, unanticipated serious adverse device effects, and 
device deficiencies. 
Sample Size: 
40 subjects  
The results of a previous clinical study on previous generations of the 
study device found that 92% of subjects had successful fixation of 
tissue after one week. It is assumed that the study device will perform 
at least as well as the 92% found previously. Therefore based on 
statistical precision, the recruitment of 36 subjects would provide with 
at least 80% probability of obtaining a 2-sided 95% confidence 
interval, around the estimate proportion of successful fixations of 
tissue, to within ±11% precision.  
With the same assumption of clinical success rate and same 
precision target, enrolling3636 subjects in ENTACT, Next Generation 
will provide probabilities between 78.4% and 90.3% of obtaining the 
2-sided 95% confidence interval of the success rate. To allow for a 
10% drop out rate, this study will enroll 40 subjects.  
Number of Study Sites: Up to 3 sites  
Targeted Global 
Regions: 
United States (US) 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 7 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Inclusion Criteria: 
The patient will be eligible for the study if he or she meets all of the 
following inclusion criteria at the baseline screening: 
1. Able and willing to give informed consent by voluntarily 
providing written informed consent in accordance with 
governing Institutional Review Board (IRB); 
2. Clinically significant deviation of the nasal septum; 
3. Willing and able to make all required study visits; 
4. Able to read and understand the approved informed consent 
form and patient reported outcome assessments (written and 
oral). 
Exclusion Criteria: 
The patient will be ineligible for the study if he or she meets any of the 
following exclusion criteria at the baseline screening or during 
surgery: 
1. Prolonged tissue approximation beyond that needed for 
normal tissue closure is necessary or desired; 
2. Traditional suturing techniques is necessary;  
3. Radiopacity is necessary or desired since ENTACT septal 
staples are radiotransparent; 
4. Known to be allergic to foreign body of materials of 
investigational product; 
5. Concomitant procedures other than turbinectomy, turbinate 
reduction, and/or sinus surgery; 
6. Pregnancy at time of the procedure; 
7. Presence of infection at the site; 
8. Severe drug and alcohol abusers; 
9. Autoimmune disease deemed clinically significant by Principal 
Investigator (PI). 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 8 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Study Duration: 
Estimated 8 months from first study site initiation to last subject last 
visit.  
Estimated enrollment period: 6 months 
Follow up period: 6 weeks 
Primary endpoint: 
At the 21-day follow-up visit, the clinician will examine the patient’s 
nasal cavity and will confirm:  
 
Septum wall straight appearance (yes/no); 
 
Complete coaptation of perichondrial flaps on septum wall 
(yes/no); 
 
Absence of significant local tissue reaction at the staple site 
(yes/no); 
 
Absence of hematoma swelling at the staple site (yes/no); 
 
No need for re-intervention at the surgery site (yes/no); 
If all the answers to the questions above are “YES” then clinical 
success will be inferred (if any answer is “NO” then repair failure will 
be inferred). 
Secondary endpoint(s): 
 
At the 5 and 42-day follow-up visit, the clinician will examine 
the patient’s nasal cavity and will confirm: 
o Septum wall straight appearance (yes/no); 
o Complete coaptation of perichondrial flaps on septum 
wall (yes/no); 
o Absence of significant local tissue reaction at the 
staple site (yes/no); 
o Absence of hematoma swelling at the staple site 
(yes/no); 
o No need for re-intervention at the surgery site (yes/no). 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 9 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
 
Assess the following intra-operative times for full population 
and by sub-groups of Septoplasty only cases and Septoplasty 
and turbinate reduction cases: 
o Total operation time for the procedure: Recorded as 
time between start of the procedure and when the 
drapes are removed from the patient, recorded in 
minutes. 
o Time for operative closure with ENTACT Septal 
stapler: Recorded as time between start of closure to 
when the stapler was handed back to the scrub nurse, 
recorded in seconds. 
 
 Nasal Obstructions Symptom Evaluation (NOSE) score 
collected at pre-op and all post-operative visits; 
 
Visual Analog Scale (VAS) pain collected at pre-op and all 
post-operative visits. 
Safety Endpoint(s) 
 
Device-related re-intervention; 
 
All adverse events (AEs) occurring from the time of surgery 
until  re-intervention or study completion; 
 
Device related AEs and serious adverse events (SAE’s); 
 
Device deficiencies (DDs). 
Other exploratory 
endpoint(s): 
 
Number and type of other Smith + Nephew devices that are 
used with the turbinate reduction adjunct procedure. 
 
 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 10 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
STUDY SCHEDULE  
Visit Type/name 
Frequency / Time point 
Screening/Pre-Operative (Visit 1) 
(≤ 30 days) Within 30 days of Visit 2 
Operative (Visit 2) 
Day 0 - Surgery 
Follow-up (Visit 3) 
Day 5±2 
Follow-up (Visit 4) 
Day 21±7 
End of Study (Visit 5) 
Day 42±7 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 11 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
CONTENTS
TABLE OF CONTENTS
Signatures ..........................................................................................................................................2
Principal Investigator Signature Page........................................................................................2
Coordinating Investigator Approval............................................................................................3
Sponsor Approval ......................................................................................................................4
Synopsis.............................................................................................................................................5
STUDY SCHEDULE................................................................................................................................10
Contents...........................................................................................................................................11
Table of Contents.....................................................................................................................11
List of Tables............................................................................................................................13
List of figures............................................................................................................................13
List of Abbreviations And definitions........................................................................................15
Introduction ......................................................................................................................................17
Background..............................................................................................................................17
Literature Summary .................................................................................................................19
Study Purpose .........................................................................................................................25
Safety Considerations..............................................................................................................25
Objective(s) ......................................................................................................................................26
Primary Objective.....................................................................................................................26
Secondary Objective:...............................................................................................................27
Safety Objective(s)...................................................................................................................27
Claims ......................................................................................................................................27
Investigational Product(s).................................................................................................................27
Identification.............................................................................................................................27
Product Use .............................................................................................................................35
Packaging and Labeling...........................................................................................................35
Product Accountability Procedures..........................................................................................35
Surgical Technique ..................................................................................................................36
Subject Enrollment and Withdrawal .................................................................................................36
Subject Population ...................................................................................................................36

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 12 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Inclusion Criteria ......................................................................................................................36
Exclusion Criteria .....................................................................................................................37
Screening.................................................................................................................................37
Informed Consent ....................................................................................................................38
Enrollment................................................................................................................................39
Screen Failures........................................................................................................................39
Lost to Follow-Up .....................................................................................................................40
Withdrawal ...............................................................................................................................40
Study Design....................................................................................................................................41
Study Design............................................................................................................................41
Allocation and Blinding.............................................................................................................43
Study Endpoints.......................................................................................................................43
Methods used to minimize bias and maximize validity ............................................................46
Study Procedures.............................................................................................................................47
Visits and Examinations...........................................................................................................47
Study Methods and Measurements .........................................................................................52
Statistical Design..............................................................................................................................53
General ....................................................................................................................................54
Analysis Populations................................................................................................................54
Baseline Data...........................................................................................................................55
Efficacy Analysis ......................................................................................................................55
Safety Analyses .......................................................................................................................57
Interim Analyses ......................................................................................................................58
Sample Size Justification .................................................................................................................58
Adverse Events and Device Deficiencies ........................................................................................58
Definitions ................................................................................................................................58
AE Coding Dictionary...............................................................................................................62
Reporting Procedures ..............................................................................................................62
Unblinding of Investigational Product ......................................................................................65
Follow-up of Subjects with Adverse Events.............................................................................65
Investigator Obligations....................................................................................................................66
Sponsor and Monitor Responsibilities..............................................................................................66

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 13 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Site Qualification Visit ..............................................................................................................67
Site Initiation Visit.....................................................................................................................67
Sponsor Audits and Regulatory Inspection..............................................................................67
Close-out Visit..........................................................................................................................67
Protocol Amendments......................................................................................................................68
Confidentiality of the Study ..............................................................................................................68
Statements of Compliance...............................................................................................................68
End of Study.....................................................................................................................................69
Publication Policy.............................................................................................................................69
Publication of Study Data.........................................................................................................69
Data Sharing ............................................................................................................................69
References.......................................................................................................................................71
Appendices ......................................................................................................................................74
Protocol Amendment ...............................................................................................................74
Instructions for use...................................................................................................................86
Equipment and Special instructions.........................................................................................86
Additional Information ..............................................................................................................86
Principal Investigator Obligations (ISO14155:2011)................................................................86
LIST OF TABLES
Table 4.2-1: Study Demographics............................................................................................................... 20
Table 4.2.1-1. ENTACT Septal Stapler Clinical Outcome Scores............................................................... 21
Table 4.2.2-1. ENTACT Septal Stapler Complications ............................................................................... 23
Table 4.4.1-1. ENTACT Septal Stapler Tolerance Limits............................................................................ 26
Table 6.1.3-1 Comparable Device Table..................................................................................................... 30
Table 6.1.4-1. ENTACT Septal Stapler Instrument Materials ..................................................................... 34
Table 9.1.1-1: Study Procedures by Visit .................................................................................................... 47
Table 12.1-1: Categories of Adverse Event ................................................................................................ 59
LIST OF FIGURES
Figure 6.1.1-1 Staple Implant Configuration (2.5mm X 4.6mm X 0.7mm) .................................................. 28
Figure 6.1.1-2. ENTACT Septal Stapler (current design) Mechanism ....................................................... 29

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 14 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Figure 6.1.3-1 Distal head changes from current device (top) to new device (bottom) .............................. 33 
Figure 8.1-1: Study Flowchart ..................................................................................................................... 42 
Figure 12.3-1: Evaluation and Reporting of AE ........................................................................................... 64 
Figure 12.3-2: Evaluation and Reporting of Device Deficiencies ................................................................ 65 
 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 15 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
LIST OF ABBREVIATIONS AND DEFINITIONS
Abbreviation
Definition
ADE
Adverse Device Effect(s)
AE
Adverse Event(s)
CE
Conformité Européene 
CAR
Clinical Activity Report
CER
Clinical Evidence Report
CSR
Clinical Study Report
CRF
Case Report Form(s)
CV
Curriculum Vitae
DD
Device Deficiency(ies)
FAS
Full Analysis Set Population
FDA
Food and Drug Administration
FU
Follow-Up
GCP
Good Clinical Practice
HIPAA
Health Information Portability Accountability Act
IB
Investigator’s Brochure
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
Investigation product
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 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 16 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Abbreviation 
Definition 
or monitoring procedures are used, and epidemiological methods are used to 
analyze the collected data. 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
ISO 
International Organization for Standardization 
NA or N/A 
Not Applicable 
N (or n) 
Total Sample Size (or subgroup sample size) 
NOSE 
Nasal Obstruction Symptom Evaluation 
NR 
Not Reported 
PMCF 
Post-Market Clinical Follow Up 
PI 
Principal Investigator 
PP 
Per-protocol Population 
S+N 
Smith + Nephew, Inc. 
SADE 
Serious Adverse Device Effect(s) 
SAE 
Serious Adverse Event(s) 
SAF 
Safety population 
SAP 
Statistical Analysis Plan 
USADE 
Unanticipated Serious Adverse Device Effect(s) 
TÜV 
Technischer Überwachungsverein/ Technical Inspection Association 
VAS 
Visual Analog Scale 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 17 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
INTRODUCTION
BACKGROUND 
In addition to olfaction, one of the main functions of the nasal passage is to provide airflow.1
Nasal airways may become obstructed, which necessitates treatment to address the blockage. 
Nasal airway obstruction may be caused by mucosal or structural defects resulting from trauma, 
idiopathic disease, or iatrogenic side effects.1 Anatomical deformities may occur in the septum, 
turbinates, or nasal valve. 
Septal deviation is one of the most common and prevalent problems in otorhinolaryngology.2 A 
deviated septum can cause nasal obstruction and is commonly treated using septoplasty.1-4
Nasal valve dysfunction may be associated with up to 13% of cases of nasal obstruction and is 
also involved in up to 95% of cases of persistent nasal obstruction after septoplasty.1
Repairing a deviated septum can be done through a surgery called septoplasty. During surgery, 
the deviated cartilage and bone are removed from the septum, leaving a dead space. 
Septoplasty involves elevation of subperichondrial/periosteal flaps bilaterally as well as resection 
and/or reshaping of the deviated cartilage and/or bone.5 The space created between the flaps 
during this procedure must be coapted in order to prevent septal hematoma and other 
complications such as abscess formation, septal perforation, or saddle-nose deformity, and 
separation of blood supply from the cartilage.1
Treatment Methods 
Septal coaptation can be performed using various treatment methods. Nasal packing materials 
have been used to approximate bilateral mucoperichondrial flaps and prevent complications 
associated with septoplasty 6-7 as well as reduce the risk of recurrent septal deviation.3,7 The 
nasal packing materials include nonabsorbable packing materials such as gauze and polyvinyl 
acetate sponge (Merocel; Medtronic Xomed) and absorbable materials such as Nasopore 
(Polyganics), and Sorbsan (Aspen Medical Europe Ltd).2 There is no consensus in the literature 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 18 of 94 
 
 
 
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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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
as to which material to use, or when the best time to remove the materials. In spite of the 
advantages, nasal packing is associated with various complications such as postoperative pain, 
continued bleeding8, worsening of sleep-disordered breathing, foreign body reaction8, and 
postoperative infection, which might result in toxic shock syndrome.7 Studies have been 
performed which utilize a local anesthetic injection perioperatively in order to reduce 
postoperative pain. In a Cochrane review performed by Fujiwara9, pain was reported to be 
reduced in the first 12 hours.  Discomfort to the patients is one of the most important 
disadvantages as it leads to an increase in the length of hospital stay.2,8 These drawbacks have 
led to the use of intranasal splints as an alternative to nasal packing. Septal splints increase 
septal stability and prevent epistaxis and synechia.2,7 However, septal splints are also 
associated with increased postoperative pain and toxic shock syndrome.10 Other methods, such 
as clips, clamps, and fibrin glue, were also used successfully to coapt septal mucosal flaps.8  
Another alternative to nasal packing is suturing. Suturing helps patients to recover from 
anesthesia quickly and easily.4 However, suture removal can cause pain and discomfort to the 
patients4. A systematic review conducted by Certal et al7. demonstrated that suturing techniques 
and nasal packing have a similar risk for postoperative hemorrhage, septal perforation, septal 
hematoma, mucosal adhesions, and location infection. However, suturing was observed to 
significantly decrease both postoperative pain, and headache compared to nasal packing in two 
systematic reviews conducted by Certal et al.7. Wang et al.4 Quinn et al.10 also conducted a 
systematic review and reported that suturing is associated with less postoperative pain 
compared to other methods of septal management such as packing and nasal splints. Although 
there are many advantages with suturing such as reduction in toxic shock syndrome, some of 
the complications and challenges associated with suturing include inability to align mucosal 
tears, breakage of needle and suture, visual limitations, and lateral nasal wall damage11. 
Suturing in a narrow nose can also be challenging and can take around 4 to 20 minutes.5   
The concept of using a stapler for coaptation of the mucoperichondrial flaps, created during 
septoplasty, has been discussed for some time in Otolaryngology. Septoplasty is one of the 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 19 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
most common procedures performed in otorhinolaryngology, and many of these procedures 
could potentially benefit from the use of septal staples. Coaptation of mucoperichondrial flaps is 
necessary following septoplasty to prevent complications associated with septoplasty. The 
ENTACT Septal Stapler has been designed to offer an option that may facilitate this step of the 
septoplasty procedure. The ability to quickly accomplish this stage of the procedure may speed 
closure, save operating room time, and may prevent inadvertent damage to surrounding tissues 
in some cases.11,5
The ENTACT stapler initially launched in 2009 by ENTrigue Surgical Inc. before the acquisition 
by ArthroCare, Corporation (now S+N). 
A summary of known and potential risks and benefits to humans of each Investigation product 
(IP) can be found in the Instructions for Use (IFU). Refer to the Instructions for Use (IFU). 
LITERATURE SUMMARY
This section aims to provide a “state of the art” review for the indications in which ENTACT (Next 
Generation) resorbable septal staple system is intended to be used per Section 4.4. A literature 
search was conducted to identify recently published articles on septoplasty.
Limitations such as language or article type were imposed in some searches for publications. 
Limiting searches to systematic reviews, a meta-analysis was performed to obtain integrated 
findings from several selected studies considered to be supportive of evidence-based practices. 
The results of these studies are discussed in terms of their general conclusions.
This section aims to identify clinical studies or usage of the current Smith & Nephew ENTACT 
Septal Stapler through an extensive literature search. 
In the current evaluation, the PubMed online database (MedLine component) and Embase were 
used to find clinical results. The medical literature was searched for an unrestricted period of 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 20 of 94 
 
 
 
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 
is contrary to the expressed or implied wishes of Smith + Nephew.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
time through July 2019. The search was performed by a qualified Evidence Evaluation 
Specialist, in July 2019. 
Four clinical studies reporting the use of ENTACT Septal Stapler in approximately 153 patients 
for septoplasty procedures were identified. Follow-up (FU) in these studies ranged from a 
minimum of one week to a maximum of 3 months.  
Table 4.2-1 summarizes the study demographics from these studies. 
Table 4.2-1: Study Demographics 
Indication 
Author, Year 
Group 
# of 
Pts 
Male 
(n) 
Mean Age 
(Range), 
Years 
Mean Follow 
up (Range), 
Weeks 
Open septoplasty 
plus turbinoplasty Sowerby
5, 2013 
ENTACT Septal 
Stapler 
8 
NR 
38** 
(18-NR) 
NR        
(NR-8) 
Septoplasty 
Sainio12, 2019 
ENTACT Septal 
Stapler 
101 
NR 
NR 
NR         
(1-12) 
Yildirim
8, 2013 
ENTACT Septal 
Stapler 
20* 
NR 
27** 
(19-34) 
NR       
(NR-3) 
Tami
13, 2010 
N/A 
24 
12 
39.9 
(20-63) 
NR        
(NR-1) 
Total: 
153 
 
(18-63) 
(1-12) 
*Estimated number of patients 
**Mean age of the entire study population      NR= Not Reported 
 
There was one prospective randomized study5, one prospective comparative study8, one 
prospective case series13, and one retrospective comparative study.12 
Yildirim et al.
8 performed a comparative study that split the patients into three treatment groups; 
group 1 had the deviated cartilage removed or repositioned, and the mucoperiachondrial flaps 
closed with an ENTACT Stapler, group 2 used suture, and group 3 were treated with Merocel 
packing. The number of patients in each group was not specifically stated; however, as the 
authors mentioned the patients were split, it can be assumed that the group sizes were equal. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 21 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Performance
Improvement in clinical outcome scores with the ENTACT Septal Stapler are reported in Table 
4.2.1-1.
Table 4.2.1-1. ENTACT Septal Stapler Clinical Outcome Scores
Indication
Author, Year
# of
Pts
Septal Coaptation 
n (%)
Nasal Obstruction Symptom 
Evaluation (NOSE)
Pre-op
Post-op
Δ
Septoplasty
Sainio12,2019
101
-
-
-
-
Open
septoplasty plus 
turbinoplasty
Sowerby5, 2013
8
-
12
2
10
Septoplasty
Tami13, 2010
24
24 (100%)
-
-
-
Septoplasty
Yildirim8, 2013
20*
-
-
-
5.7 ±
0.923
*Estimated number of patients
Δ Change from preop to postop scores
Approximately 153 patients have undergone septoplasty using the ENTACT Septal Stapler in 
four studies5,13,8,12 Sowerby et al.5 conducted a prospective randomized study and reported a 
significant decrease in the mean operation time in the ENTACT Septal Stapler group compared 
to the quilting sutures group (28 ± 6 minutes vs. 43 ± 13 minutes respectively; p=0.014). The 
mean time for septal closure was also reported to be significantly lower in the ENTACT Septal 
Stapler group than the quilting suture group (35 ± 22 seconds vs. 420 ± 70 seconds; p<0.001).5
In a prospective case series conducted by Tami et al.13 the amount of time taken to apply 
staples from the ENTACT Septal Stapler was reported to be <60 seconds5. Sainio et al.12
conducted a retrospective comparative study comparing ENTACT Septal Stapler to the non-
stapler group where silicone splints, tamponade, or sutures were used during septoplasty. 
Sainio et al.12 observed no significant difference in the mean operation time between the 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 22 of 94 
 
 
 
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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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
ENTACT Stapler group and the non-stapler group (63.9 minutes vs. 64.3 minutes, 
respectively).12 
A significant improvement in Nasal Obstruction Symptom Evaluation (NOSE) scores 
postoperatively at a 3 week follow up was also observed by Sowerby et al.5 with an improvement 
of 10 and a postoperative score of 2 (p<0.001). NOSE scores also decreased postoperatively. 
However, no significant difference was observed between the groups, and the mean difference 
was reported to be 5.7 ± 0.923 in the ENTACT stapler group vs. 5.90 ± 0.641 in the suture group 
vs. 6.2 ± 0.62 in the Merocel group.8 Nasal Obstruction Symptom Evaluation (NOSE) 
questionnaire assists in quantifying the severity of a patient’s nasal congestion. The severity is 
rated on a 0-4 scale with 0 representing “no problem” and 4 representing “severe problem” in 
five categories, resulting in a maximum score of 20 for patients with severe obstruction. The 
NOSE scale was based on a max score of 20 for Sowerby et al.5 and not reported in Yildrim et 
al.8 The NOSE scale is commonly used to evaluate nasal obstruction following 
septoplasty.5,19,8,16 In patients with nasal obstruction caused by septal deviation, a reduction in 
nasal airway obstruction following septoplasty can be used as one of the indicators of successful 
completion of the procedure.  
Tami et al.
13 conducted a prospective, case series evaluating the performance and safety of 
ENTACT Septal Stapler in 24 patients and reported complete coaptation in 100% of the patients 
at a one week follow up. 
Yildirim et al.
8 conducted a prospective, comparative study, comparing ENTACT Septal Stapler 
to 4/0 Pegelak (Dogsan TR) sutures, and Merocel nasal packs in patients undergoing 
septoplasty for deviated septum. A total of 60 patients were included in the study. Yildirim et al.
8 
measured patient comfort using Visual Analog Scale (VAS) scores two days postoperative. 
Visual Analog Scale (VAS) scores were used to evaluate patient comfort on a scale of 0-4 with 0 
representing poor and 4 representing excellent. Although postoperative VAS scores decreased, 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
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Version: 2.0, 27Aug2020
Page: Page 23 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
no significant difference was observed between the groups. Postoperative (2 days) VAS scores 
were significantly lower in the nasal packing group compared to their preoperative VAS scores 
(P<0.05). The authors concluded that nasal packing had a negative impact on patient comfort 
compared to no packing. Mean difference in the VAS scores was reported to be 4.1 ± 0.97 in
the ENTACT stapler group vs. 4.15 ±1.31 in the suture group vs. 6.4 ± 1.43 in the Merocel 
group.
8
Safety
Complications identified in the four clinical publications are reported in Table 4.2.2 -1.
Table 4.2.2-1. ENTACT Septal Stapler Complications
Author, Year
# of 
Pts
Perforation 
(n)
Hematoma 
(n)
Edema (n)
Inflammation 
(n)
Infection 
(n)
Sainio12,2019
101
1
1
-
-
6
Sowerby5, 2013
8
1
-
2
-
-
Tami13, 2010
24
-
-
-
5
-
Yildirim8, 2013
20*
-
-
-
-
-
Total
153
2
1
2
5
6
*Estimated number of patients
Device related complications were reported in three studies.5,13,12 Perforation was reported in 
two studies.5,12 Sainio et al.12  reported perforation in 1 patient (0.99%) in the ENTACT Stapler 
group and a reoperation was performed in this patient. Sowerby et al.5 reported a 1 mm 
postoperative perforation occurred in one patient (12.5%) due to jamming of the ENTACT Septal 
Stapler (2009) and stated that this can be avoided with the newer model (2010/2012) of the 
stapler. Perforation was in line with other outcomes reported in the State of the Art for alternative 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 24 of 94 
 
 
 
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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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
devices for the Sainio12 study. In Sowerby et al.5, the authors concluded that the septal stapler 
can be used without an increased morbidity in comparison to suture closure or impact to 
subjective patient scores.   
 
Tami et al.13 reported that the first lot of ENTACT Septal Staplers (2009) failed to perform to 
design specifications and only four total staples from three staplers were implanted in one 
patient.  
 
Sainio et al.12 observed haematoma in one patient in the ENTACT Stapler group. Sainio et al.12 
reported that perforation and haematoma, which occurred at a low rate of 1% each in the study, 
is in agreement with the study conducted by Tami et al.13 and stated that “ENTACT Septal 
Stapler is safe to use”.  The complications reported in the four studies of the ENTACT stapler 
are performing in-line with alternative devices on the market as discussed in the State of the Art.  
 
Some of the minor complications observed in the literature were edema, inflammation and 
infection. Sowerby et al.5 conducted a prospective, randomized clinical study comparing 
ENTACT Septal Stapler to quilting sutures in patients undergoing septoplasty. Sowerby et al5 
observed mild edema in 2 patients in both the groups at a 3 week follow up. However, the 
edema resolved in 2 months. In a prospective, case series13, mild inflammation was reported at 
a 1 week follow up in 21% of the patients in whom ENTACT Septal Stapler was used for 
approximation of mucoperichondrial flaps after septoplasty whereas no inflammation was 
observed in 79% of the patients. Expected rates of edema or inflammation following septoplasty 
were not discussed in the four publications identified. Other complications reported in the 
literature include bleeding,12 and fever.12  
 
Sainio et al.12 conducted a retrospective comparative study comparing ENTACT Septal Stapler 
to the non-stapler group where silicone splints, tamponade, or sutures were used during 
septoplasty. No significant difference in the complication rate was observed between the 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 25 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
ENTACT Septal Stapler group (9.9%) and the subgroups such as silicone splint group (9.7%), 
suture group (12.7%), and the tamponade group (9.5%) in the non-stapler group.12
Since the ENTACT (Next Generation) Septal Stapler utilizes the same staples and a similar 
delivery mechanism to the previous ENTACT Septal Stapler, it is anticipated that the Next 
Generation device will perform the same as the previous generation device.
STUDY PURPOSE
To provide evidence to satisfy the PMCF requirements of Conformité Européene (CE) marking
to market this device in Europe (data may be used to support registrations on other countries as 
well). 
SAFETY CONSIDERATIONS
The ENTACT Septal Stapler delivers implantable septal staples that are intended to connect 
internal tissues to aid healing and for approximation of soft tissue during nasal surgery. 
Representative language of the contraindications and potential adverse effects from the 
ENTACT Septal Stapler can be found in the instructions for use (IFU). The ENTACT Septal 
Stapler are supplied sterile. The ENTACT stapler is sterilized using Gamma Irradiation.14,15
Potential Adverse Effects listed in the IFU include:

Possible adverse effects include but are not limited to wound complications, including 
hematoma, site drainage, infection, toxic shock syndrome, and other complications that 
are possible with any surgery.

When implanted, the ENTACT Staple may elicit a minimal tissue reaction characteristic 
of foreign body response to a substance. The tissue reaction resolves as the material is 
absorbed.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 26 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols

Fracture or extrusion of the ENTACT Staple, with or without generation of particulate 
debris.
Tolerance limits for potential adverse effects derived from literature
Based on the state of the art data in Table 4.2.2-1 and Section 4.2.2 the expected tolerance 
limits for potential adverse effects from literature in the ENTACT Septal Stapler system are
stated in Table 4.4.1-1.
Table 4.4.1-1. ENTACT Septal Stapler Tolerance Limits
Expected Complications 
(derived from literature)
Tolerance limits 
from literature
Tolerance limits to show no significant 
difference from literature* (maximum 
allowed)
Perforation
2/153 (1.31%)
2/40 5% (95% CI 0.6% to 16.92%)
Hematoma
1/153 (0.65%)
2/40 5% (95% CI 0.6% to 16.92%)
Edema 
2/153 (1.31%)
2/40 5% (95% CI 0.6% to 16.92%)
Inflammation 
5/153 (3.27%)
4/40 10% (95% CI 2.8% to 23.7%)
Infection 
6/153 (3.92%)
4/40 10% (95% CI 2.8% to 23.7%)
* These numbers have been derived based on the study sample size of N=40.
Actual study adverse events occurrences will be reviewed under Section 10.5 and Section 12 
and assessed relative to the tolerance limits.
OBJECTIVE(S)
The primary, secondary, and safety objectives of this study are listed as follows.
PRIMARY OBJECTIVE
The primary objective of this study is to demonstrate clinical success of the ENTACT (Next 
Generation) resorbable septal staple system by examining the patient’s nasal cavity at the 21 
day follow up visit.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 27 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
SECONDARY OBJECTIVE:                                             
The secondary objectives are to generate performance and health economics supporting the 
use of ENTACT (Next Generation) resorbable septal staple.                                            
SAFETY OBJECTIVE(S)
Assess safety with reported complications, adverse events, adverse device effects, 
unanticipated serious adverse device effects, and device deficiencies (DD). 
CLAIMS
The proposed Marketing Claims for this study include, but are not limited to, the following:

Approximation of septal flaps is achieved in less than a minute;

ENTACT septal stapler saves time in the operating room compared to traditional suturing 
techniques.
INVESTIGATIONAL PRODUCT(S)
IDENTIFICATION
Investigation Product
The ENTACT Septal Stapler delivers implantable ENTACT septal staples which are intended to 
connect internal tissues to aid healing and for approximation of septal flaps of soft tissues during 
nasal septal surgery. The ENTACT Septal Stapler consists of resorbable fixation devices, which 
are delivered via a manual surgical stapler delivery system. Each sterile, single patient use 
device contains eight ENTACT septal staples for holding the septal tissues together during post-
op healing.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
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Version: 2.0, 27Aug2020 
Page: Page 28 of 94 
 
 
 
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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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
The ENTACT staple is designed to resorb in about 3 to 6 weeks when used according to 
labeling
14,15. The staples shown in Figure 6.1.1-1 are made up of poly(L-lactide-co-glycolide) 
(PLG), which has an extensive history of use in medical applications. They are biodegradables 
that degrade into natural compounds found in the body and are easily eliminated through normal 
physiological pathways
1. 
Figure 6.1.1-1 Staple Implant Configuration (2.5mm X 4.6mm X 0.7mm)  
                                      
 
The distal tip of the ENTACT Septal Stapler mechanism shown in Figure 6.1.1-2 displays the 
primary mechanical components. The preloaded implants are stacked in a holding block. The most 
distal implant is deployed by a Nitinol ribbon that is advanced when the trigger is pulled. Once the 
distal implant has exited the implant holding block, the next implant is indexed into position by the 
force generated by a spring. 
The ENTACT Septal Stapler, with the aid of a piercing needle at the tip of the Nitinol ribbon, is 
designed to deploy the staple with sufficient force to penetrate the mucoperichondrial tissue, with 
or without cartilage reinserted. The removable tab is a safety mechanism to restrain the spring 
tension off the implants during storage and to prevent jamming prior to implantation. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 29 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Figure 6.1.1-2. ENTACT Septal Stapler (current design) Mechanism
ENTACT Septal Stapler (Previous generations)
The ENTACT stapler originally launched in 2009 by ENTrigue Surgical Inc before the acquisition 
by ArthroCare (now S+N). Feedback from the market was collected, and changes to the device 
were implemented in 2010 and 2012. The changes were implemented to streamline the 
manufacturing process and improve device functionality.
ENTACT Septal Stapler (Next Generation)
The Next Generation device seeking CE marking utilizes the same implant as the current 
version of ENTACT Septal Stapler. The implant’s material composition, geometry, and 
processing remain unchanged. The delivery system is very similar in the new device, with a few 
changes to the delivery part of the device in order to enhance manufacturability and reduce the 
cost of goods. A comparison of the current vs. new design ENTACT Septal Stapler can be found 
in Table 6.1.3-1.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 30 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Table 6.1.3-1 Comparable Device Table 
Current Design 
Previous generation 
New Design 
 Next Generation 
Impact of 
Differences 
Implant Design 
 
The ENTACT staple is ~4.6 mm long, ~2.5 mm wide and 
~0.55 mm thick in the shaft middle but ~0.7 mm thick at 
the top and bottom tabs. 
None 
Implant composition 
Polymer: 
L-lactide-co-glycolide 
L-Lactide/Glycolide Content: 
5/95 ratio 
Inherent Viscosity 
1.6 ± 0.4 dL/g 
Water content: 
≤ 0.5% 
D&C Violet #2: 
0 – 0.10% wt% 
Monomer Content: 
<5.0% total 
None 
Height of Distal head 
Width of Distal head 
8.3mm 
6.0mm 
7.0mm 
4.9mm 
None, 
justification below 
Counter tension arm 
material 
Medical grade 
Polycarbonate and 
17-4 Stainless steel 
Ixef 1022 PARA 
(polyacrylamide with 
50% glass fiber) 
None, justification 
below 
Implant channel material 
304 Stainless steel 
None 
Holding block material 
Medical grade Polycarbonate 
None 
Pins in channel material 
18-8 Stainless steel 
300 Series Stainless steel 
None, 
justification below 
Push ribbon material 
Nitinol 
None 
Pull ribbon material 
Nitinol 
None 
Sterilization 
Gamma Irradiation 
None 
 
Current Design 
Previous Generation 
New Design 
Next Generations 
Impact of 
Differences 
Packaging 
configuration 
Foil pouch, Carton 
None 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 31 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Indications 
The ENTACT Septal Stapler delivers implantable septal 
staples which are intended to connect internal tissues to 
aid healing and for approximation of soft tissues during 
nasal septal surgery 
None 
Surgical Technique/ 
Deployment Methods 
1. If there is no cartilage between the mucoperichondrial 
flaps, the staples can be delivered unilaterally. If 
cartilage is present, stapling the flaps bilaterally may be 
considered. 
2. Remove protective silicone cover from the distal end 
of the stapler. 
3. Unfold and gradually remove pull tab from the distal 
end of the stapler. 
4. Insert the distal tip of the ENTACT Septal Stapler in 
the nose, one arm in each nostril. 
5. Plan placement of staples, so they are spaced 
approximately 15 mm apart or as deemed necessary 
from each other. 
6. Place the stapler against the mucoperichondrial flap, 
keeping stapler as perpendicular to the tissue surface as 
possible and depress handle until an audible click is 
heard to deploy each staple. 
7. Release handle until a second audible click is heard 
before repositioning the distal tip of the stapler. 
8. If necessary, repeat this procedure in the 
opposite cavity. 
9. Visually inspect both nasal cavities to assure adequate 
approximation and sufficient penetration of the staples. 
10. The device is empty when the blue indicator within the 
clear implant housing is against the distal tip. Firing an 
empty device will cause the implant guide needle to pierce 
and make a hole in the septum without placement of an 
implant. 
11. When complete, dispose of stapler with any remaining 
staples. 
 None 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 32 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
The Next Generation Smith+Nephew ENTACT Septal Stapler described in Table 6.1.3-1 
can be considered comparable to the Previous Generation of the ENTACT Septal Stapler 
for the following reasons: 
 
Clinical 
o Both devices are indicated for connecting internal tissues to aid healing and 
for approximation of soft tissues during nasal septal surgery. 
 
Technical 
o Both devices enable septal flap closure through the delivery of resorbable 
implants. 
o The mechanism and kinematics used to deploy the staples are the same in 
both devices. The principles of operation are identical. 
 
Biological: 
o The materials utilized in the implant, implant channel, holding block, and the 
push and pull ribbon are exactly the same in both devices. 
Below are the identified differences between the Next and Previous Generation ENTACT 
Septal Stapler with a rationale for acceptance of those differences. 
 
Clinical: 
o None, both devices have the same intended use. 
 
Technical: 
o Distal head changes - the height of the distal head was 
reduced from 8.3mm to 7.0mm, and the width was reduced 
from 6.0mm to 4.9mm. The minor design changes to 
improve surgical access do not affect the intended use of 
the device. 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 33 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Figure 6.1.3-1 Distal head changes from current device (top) to new device 
(bottom)
o

Biological
o
Counter tension arm - There are no impact of differences in material for the 
counter tension arm as PARA has mechanical properties close to stainless
steel, and is commonly used in medical devices. Smith+Nephew has
conducted both biological and mechanical testing, and has objective evidence
that the new device meets all the same requirements as the current device.
o
Pins in Channel - There are no impact of differences in material for the pins in
channel as 18-8 stainless steel are in the 300 series stainless steel family, 
with different naming conventions. These designations are considered
interchangeable as 300 Series stainless steels are required to contain 18% 
chromium and 8% nickel and 18-8 means the steel is 18% chromium and 8% 
nickel. Smith+Nephew has conducted both biological and mechanical testing, 
and has objective evidence that the new device meets all the same 
requirements as the current device.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 34 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
The minor differences between the comparable device previous generation ENTACT Septal 
Stapler and Next Generation ENTACT Septal Stapler, are expected to have no impact to 
the safety of the devices. As these devices as considered comparable, we expect similar 
clinical safety and performance outcomes.
Refer to the ENTACT Septal Stapler Instructions for Use for more information.  
Do NOT place a staple where the needle path is obstructed or a collision with any object 
may occur.
Do NOT use the staple on tissue which is too thick or hard (such as bone) to permit an 
effective tissue capture.
Do NOT use with patients in whom radiopacity is necessary or desired since ENTACT 
staples are radiotransparent.
Do NOT use in patients in whom prolonged tissue approximation beyond that needed for 
normal tissue closure is necessary or desired.
Material Specification Staple Implant
The staple implant configuration is composed of the absorbable copolymer 5% Poly-L-lactide / 
95% Polyglycolide. During the molding process, a violet colorant is introduced. The D&C Violet 
#2 is a colorant additive (~ 0.05 wt%) to make the implants easier for the doctor to visualize 
upon placement in the tissue. As previously stated, the ENTACT staple used in both the current 
and subject devices are identical.
Table 6.1.4-1. ENTACT Septal Stapler Instrument Materials
Description
Existing Device 
Material
(Previous Generation)
New Device Material 
(Next Generation)
Categorization
Nature of Body 
Contact
Contact 
Duration
Counter tension arm
Medical grade
Polycarbonate and 17-4 
Stainless steel
Ixef 1022 PARA
(polyacrylamide with 
50% glass fiber)

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 35 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Implant channel
304 Stainless steel
Surface contact – skin 
and mucosal 
membranes
Transient
Holding block
Medical grade Polycarbonate
Pins in channel
18-8 Stainless steel
300 Series Stainless
steel
Push ribbon Pilot 
Hole ribbon
                                  Nitinol
Ancillary Product
Not applicable (NA)
PRODUCT USE
Refer to IFU for detailed information on contraindications, warnings, precautions, intended users, 
physician training requirements, instructions for use, and device disposal. 
Sites that are familiar with the use of ENTACT Septal Stapler will be selected; no additional 
training is required.
PACKAGING AND LABELING
Packaging and labeling will be prepared to meet regulatory requirements.
Labeling of Investigational Product
All devices used in this study will be procured in standard commercial packaging, ordered via 
normal and customary Smith + Nephew procedures, and managed per study site processes.
PRODUCT ACCOUNTABILITY PROCEDURES 
The investigational product (IP) is not provided by S+N for this post-market study, and no 
product accountability procedures will be applied. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 36 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
SURGICAL TECHNIQUE
All study-related procedures with the ENTACT Septal Stapler must be performed according to 
the recommended surgical technique described in the protocol or in a separate instructional 
document and product labeling (e.g., IFU) as applicable.
Surgeons selected to participate in this study will be familiar with using the ENTACT Septal 
Staples system.
SUBJECT ENROLLMENT AND WITHDRAWAL
SUBJECT POPULATION
The study will consist of five visits, including screening/pre-operative, operative, and follow up 
visits at 5, 21, and 42 days post-surgery. The need for these visits as part of the study will be 
made clear in the consent form and will be fully explained at the time of recruitment. 
Forty (40) individuals to be approached for participation in this study awho are receiving or 
seeking care for nasal septal obstructions. Subjects will be enrolled up to 3 sites across the 
United States. 
Ethnic minorities are classed as vulnerable subjects according to International Organization for 
Standardization (ISO) 14155:2011; however, they will be included providing they meet other 
inclusion criteria, and there are informed consent documents and personnel to lead the consent 
process in a language that is fully understood by the potential subject. 
INCLUSION CRITERIA
The patient will be eligible for the study if he or she meets all of the following inclusion criteria at 
the baseline screening:

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 37 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
1. Able and willing to give informed consent by voluntarily providing written informed 
consent in accordance with governing Institutional Review Board (IRB);
2. Clinically significant deviation of the nasal septum;
3. Willing and able to make all required study visits;
4. Able to read and understand the approved informed consent form and patient 
reported outcome assessments (written and oral).
EXCLUSION CRITERIA
The patient will be ineligible for the study if he or she meets any of the following exclusion criteria 
at the baseline screening or during surgery:
1. Prolonged tissue approximation beyond that needed for normal tissue closure is 
necessary or desired;
2. Traditional suturing techniques is necessary;
3. Radiopacity is necessary or desired since ENTACT septal staples are 
radiotransparent;
4. Known to be allergic to foreign body of materials of investigational product;
5. Concomitant procedures other than turbinectomy, turbinate reduction and/or sinus 
surgery;
6. Pregnancy at time of procedure;
7. Presence of infection at the site;
8. Severe drug and alcohol abusers;
9.
Autoimmune disease deemed clinically significant by Principal Investigator.
SCREENING 
Subjects will be recruited for the study through the clinical practices of the Investigators. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 38 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
40 individuals to be approached for participation. Subjects will be enrolled as they meet eligibility 
and consent to the study.  
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 Enrollment Log. 
All screening activities that occur prior to consent shall be referred to as pre-screening.
Any subject that meets the definition of a Vulnerable Subject [per International Organization for
Standardization (ISO) 14155:2011 Section 3.44.] should be reviewed, but not excluded from the
study.
INFORMED CONSENT
Before conducting any study procedures or examinations, informed consent shall be obtained
from all participants according to ISO14155 guidelines, the Health Insurance Portability and 
Accountability Act (HIPAA, if applicable), and local regulations. Patients must be informed as to 
the purpose of the study and the potential risks and benefits known or that can be reasonably
predicted or expected as described in the written Informed Consent Form (ICF). The patients
shall have sufficient opportunity to consider participation in the study. Patients will then be 
invited to read, sign and personally date the Institutional Review Board (IRB)-approved ICF, 
indicating their consent for enrollment. Additionally, the individual who obtains consent from the 
participant will sign and date the ICF. A copy of the signed informed consent documentation will 
be provided to the participant, and the original filed in the investigator site file (ISF).
In the case of vulnerable subjects, the ICF must be understood and signed by the subject’s 
legally authorized representative (parent or legal guardian). Assent to participate in the study 
should be obtained for subjects ≥7 years of age and <18 years of age if allowed by local 
regulations. For subjects less than 7 years of age an assent will not be obtained.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 39 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
In the case of minors, the ICF must be obtained by their legally designated representative.  The 
minor shall participate in the informed consent process in a way suitable for his/her age and 
mental maturity. Minors will receive the study information in a way adapted to their age and 
mental maturity from investigators or members of the investigating team who are trained or 
experienced in working with children. If minors express a wish or an opinion with regards to 
study participation this needs to be respected by the Investigator. If during the study, the minor 
reaches the age of 18 years (legal competence), the informed consent shall be obtained again, 
before the subject can continue to participate in the clinical investigation.
Study research staff may then complete Visit 1 Initial Visit (Screening/ Pre-Operative) with the 
subject. If a subject refuses participation, no further information will be collected. Reason for 
exclusion should be noted on the Screening and Enrollment Log.
ENROLLMENT
Subjects for whom the consent process has been completed and have been treated with the 
study product are considered enrolled.
Subjects will be assigned a Subject ID at the time of consent.
SCREEN FAILURES
Subjects who have provided consent, completed screening, and for any reason do not meet the 
eligibility criteria, were not enrolled by the Investigator for any reason, or withdraw consent for 
any reason prior to enrollment, will be considered a consented screen failure. For these
subjects, record the reason for screen failure on the Screening and Enrollment Log and 
complete the End of Study Case Report Form (CRF) documenting the primary reason for 
discontinuation. Consented screen failures will be replaced without limit by newly enrolled 
subjects.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 40 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
LOST TO FOLLOW-UP
A subject will be considered lost to follow-up if he/she does not appear for the scheduled study 
visit for two consecutive visits and does not return for a final 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 before declaring a subject to be lost to follow-up (LTFU): the subject has been 
contacted according to the site's policies, but no fewer than two documented phone contacts 
and one certified letter without response. Copies of all attempts to reach the subjects by mail or 
email and/or the attempts to contact the subject via other means should be documented, and 
that documentation should be kept with the subject’s source documents at site. 
WITHDRAWAL
All reasonable efforts should be made to collect 42 day postoperative data on all subjects 
enrolled in this study. 
Withdrawal from Treatment
The Investigator may withdraw subjects from the study for many reasons, including but not 
limited to, the following:

subject noncompliance (e.g., did not follow instructions);

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;

Adverse Events/Adverse Device Effects that affect the ability to evaluate the study 
product without bias;

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 41 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols

any other significant reason identified by the Investigator;

re-intervention.
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 drop out or are withdrawn will not be re-entered into the study at a later date. 
Subject’s Withdrawal of Consent to Participate in 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 respecting the subject’s privacy. The 
reason for withdrawal will be recorded in the CRF and source documents.
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. 
STUDY DESIGN
STUDY DESIGN
This is a prospective, multi-center, single arm PMCF study to evaluate the safety and 
performance of the ENTACT (Next Generation) resorbable staple system for septoplasty in 40
subjects. The study purpose is to provide evidence to satisfy the PMCF requirements of CE 
Marking to market this device in Europe (data may be used to support registrations on other 
countries as well).   
This study will enroll at up to 3 clinical sites in the United States.  

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 42 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
This is an open-label study with consecutive enrollment. The study will continue for 6 weeks
from the date that the last subject received the study treatment to the date that the last subject
completes the study as planned. Only subjects who meet the enrollment criteria as listed in 
section 7 will be enrolled in the study. The study duration is an estimated 8 months from first 
study site initiation to last subject last visit. 
Figure 8.1-1: Study Flowchart 
Visit 1: 
Screening/Pre-
Operative               
(≤ 30 days )
-Informed Consent
-Inclusion/ 
Exclusion
-Patient 
Demographics: 
Medical History
-Concomitant 
Medications, 
Procedures
-PROs: NOSE, VAS
Visit 2 :       Surgery 
(Day 0)
-Record device 
identification
-Operative 
-Discharge 
-Concomitant 
Medications, 
Procedures
-Safety 
Assessment 
(AE/SAE/ADE/DD)
-End of 
Study/Subject 
Disposition  (if 
applicable)
Visit 3:
FU time point  
(Day 5±2)
-Nasal 
examination
- PROs: NOSE, VAS                      
-Concomitant 
Medications, 
Procedures
-Safety 
Assessment 
(AE/SAE/ADE/DD)
-End of 
Study/Subject 
Disposition  (if 
applicable)
        
Visit 4:
FU time point           
(Day 21±7)
-Nasal examination
-PROs: NOSE, VAS
-Concomitant 
Medications, 
Procedures
-Safety Assessment 
(AE/SAE/ADE/DD)
-End of 
Study/Subject 
Disposition (if 
applicable)
Visit 5:
FU time point 
Day 42±7
-Nasal 
examination
-PROs: NOSE, 
VAS
-Concomitant 
Medications, 
Procedures
-Safety 
Assessment(AE/S
AE/ADE/DD)
-End of 
Study/Subject 
Disposition 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 43 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
ALLOCATION AND BLINDING
Treatment Allocation
This study is not randomized. Subjects will be enrolled with the ENTACT (Next Generation) 
Septal Stapler system.
Blinding
The study is not blinded. 
STUDY ENDPOINTS
Primary Endpoint
At the 21-day follow-up visit, the clinician will examine the patient’s nasal cavity and will confirm:

Septum wall straight appearance (yes/no);

Complete coaptation of perichondrial flaps on septum wall (yes/no);

Absence of significant local tissue reaction at the staple site (yes/no);

Absence of hematoma swelling at the staple site (yes/no);

No need for re-intervention at the surgery site (yes/no);
If all the answers to the questions above are “YES” then clinical success will be inferred (if any 
answer is “NO” then repair failure will be inferred). 
Secondary Endpoints 

At the 5, and 42-day follow-up visit, the clinician will examine the patient’s nasal cavity 
and will confirm:
o
Septum wall straight appearance (yes/no);
o
Complete coaptation of perichondrial flaps on septum wall (yes/no);

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 44 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
o
Absence of significant local tissue reaction at the staple site (yes/no);
o
Absence of hematoma swelling at the staple site (yes/no);
o
No need for re-intervention at the surgery site (yes/no);

Assess the following intra-operative times for full population and by sub-groups of 
Septoplasty only cases and Septoplasty and turbinate reduction cases:
o
Total operation time for the procedure: Recorded as time between start of the 
procedure and when the drapes are removed from the patient, recorded in 
minutes
o
Time for operative closure with ENTACT Septal stapler: Recorded as time 
between start of closure to when the stapler was handed back to the scrub nurse, 
recorded in seconds.

NOSE score collected at pre-op and all post-operative visits;

VAS pain collected at pre-op and all post-operative visits.
Safety Endpoints
Following are the safety endpoints for this study:

Device-related re-intervention;

All adverse events (AEs) occurring from the time of surgery until re-intervention or study 
completion;

Device related AEs (ADEs) and serious adverse events (SAE’s);

Device deficiencies (DDs)
All AEs will be categorized in terms of seriousness and relatedness to the study device or to the 
surgical procedure. All Serious Adverse Device Effects will be further categorized as Anticipated 
or Unanticipated. The definitions for each of these categories are based on ISO 14155:2011.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 45 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Exploratory Endpoints
Exploratory endpoints proposed, but not limited to, the following:

Number and type of other S+N devices with the turbinate reduction adjunct procedure 
Balanced Covariates
The inclusion/exclusion criteria will be generalizable and applicable to the widest possible subset 
of the population needing septoplasty. These criteria will be uniformly applied so as to enroll a 
cohort of subjects with similar symptoms and clinical requirements. This should maximize the 
applicability to as many subjects with similar baseline characteristics and help to bolster external 
validity.
Subject Attrition
Subject attrition due to reduction in sample size required for precision analysis has been 
accounted for in the sample size calculation so that the estimate of the Confidence Interval (CI) 
to be obtained will still be valid through the most efficient use of available subjects.
Pre-specification of Statistical Analysis 
The primary outcome measure has been pre-specified as well as the type of statistical analysis 
to be performed to evaluate procedure success rate so as to minimize reporting bias. The 
precision analysis planned for the study, which includes construction of confidence intervals for 
the outcome summaries and a pre-defined range in which the 95% CI for the primary outcome 
are expected to fall within are designed to maximize the validity of the study results.
More detailed information on analyses to be carried out will be incorporated in the Statistical 
Analysis Plan (SAP) so as minimize any threats to external validity in order to yield clinically 
relevant estimates of effects and precision.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 46 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
METHODS USED TO MINIMIZE BIAS AND MAXIMIZE VALIDITY
Multi-center
The samples from multi-center are more representative than those from single center, and the 
latter may lead to deviation of study results due to its systematic errors. The required number of 
cases can be enrolled in a shorter period, and the samples are more representative and the 
results are more generalizable. 
In this study, subjects will be enrolled at multiple sites, utilizing up to 3 US sites. This will reduce 
the effect of observer bias that might arise at any one investigational site as well as maximize 
the diversity of subjects treated.
Screening of Subjects
In order to eliminate selection bias, the Investigators will continuously screen all subjects. 
Subject recruitment continues until the completion of subject recruitment.
Investigator Training
Prior to the clinical trial, the clinical research associate (CRA), coordinating with the persons in 
charge of the study sites, will train the Investigators on the study protocol, making sure they are 
familiar with the use of investigational medical device, and implement subject enrollment strictly 
in accordance with the inclusion criteria and exclusion criteria, conduct relevant examinations 
according to the protocol requirements, also master all new device-related information found 
during the clinical trial, thus to minimize the interferential factors. The follow-up exams will be 
delegated to Investigators not involved in the procedure to reduce potential bias by the surgeon. 
Clinical Trial Monitoring
Detailed monitoring requirements will be documented in the Clinical Monitoring Plan for this 
study. The monitor is selected and appointed by the Sponsor to conduct a regular on-site 
monitoring visit, making sure that all contents in the study protocol are strictly followed. The

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 47 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
source documents are inspected to ensure consistent contents with the CRF. Monitoring visits 
will be conducted at the start, during and at the closure of the clinical study in accordance with 
Smith+Nephew standard operating procedures (SOPs) and the Clinical Monitoring Plan.
STUDY PROCEDURES
VISITS AND EXAMINATIONS 
None of the listed activities are undertaken by Sponsor personnel.
Table 9.1.1-1: Study Procedures by Visit
Schedule of Events
Patient screening and 
surgery
Post-operative patient visits
Screening/Pre-
Operative
≤ 30 days 
Surgery
Day 0
FU time point 
Day 5±2
FU time point
Day 21±7
FU time point
Day 42±7
Informed Consent
X
-
-
-
-
Inclusion/Exclusion
X
-
-
-
-
Demographics: Medical 
History
X
-
-
-
-
Operative data (Intra-
operative delivery 
success, intra-
operative time to 
deploy staples to 
complete septoplasty)
-
X
-
-
-
Discharge data
-
X
-
-
-
Visual assessment of 
nasal cavity
-
-
X
X
X
NOSE score
X
-
X
X
X
Visual Analog Scale
X
-
X
X
X
Concomitant 
Medications, 
Procedures
X
X
X
X
X
Safety assessment 
(AE/SAE/ADE/DD)
-
X
X
X
X

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 48 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
End of Study/Subject 
disposition
-
*
*
*
x
*As needed
Post-operative visits:
(1) Day 5±2 covers the true “fixation” period for initial healing
(2) Day 21±7 covers the standard of care for patient follow-up
(3) Day 42±7 covers the clinical follow-up duration associated with the lifetime of the device
Notes:
Subjects who have undergone a re-intervention procedure of the implant will be considered 
terminated from the study from the date of the re-intervention. Study related data will not be 
collected following the date of the re-intervention.
All concomitant medications/ procedures including any associated with an AE, SAE or SADE 
will be recorded.
Screening/Preoperative Visit (Visit 1)
Below are the procedures that will be done at the Screening/Preoperative visit.
NOTE: Any subject who signs an informed consent/assent but fails to meet the required entry 
criteria is considered to be a consented Screen Failure. 
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, including information on all 
concomitant medications/therapies. 
3.
Screen the subject for protocol inclusion/exclusion criteria. 
4.
Assign the subject a Subject ID.
5.
Complete Screening and Enrollment Log.
6.
Complete NOSE score assessment and VAS pain score.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 49 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
7.
Subjects will be instructed to return for the Operation Visit (Procedure) as scheduled by 
the site.  
Treatment/Operation Visit (Visit 2)
1.
Query subject regarding any changes in general health and the use of concomitant 
medications.
2.
Commence treatment/operation.
3.
Confirm eligibility criteria
4.
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. Also 
record concomitant medications/therapies used to treat AEs.
5.
Record Intra-operative delivery success, total operation time and Intra-operative time for 
operative closure with ENTACT septal stapler.
6.
Record device identification information for the stapler (e.g., Unique Device Identifier,
Lot Number, Serial Number, Catalogue Number) and the number of staples used.
7.
Instruct the subject on proper postoperative care/procedures, including any 
contraindicated treatments/medication(s).
8.
9.
Instruct the subject on follow-up procedures, including returning the treatment facility in 
5 days (± 2) days for follow-up visit.
Complete Operation and Discharge Visit CRFs.
10
If applicable, complete an End of Study CRF.
Follow-up Visit (Visit 3) Day 5 (± 2 days)
1.
Query subject regarding any changes in general health and the use of concomitant 
medications.
2.
Record assessment of nasal cavity.  

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 50 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
3.
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. Also record concomitant medications/therapies used to treat AEs.
4.
Complete NOSE score assessment and VAS pain score.
5.
Instruct the subject on follow-up procedures, including returning the treatment facility 
at 21 days post-operative (± 7) days for follow-up visit.
6.
If applicable, complete an End of Study CRF.
Follow-up Visit (Visit 4) Day 21 (± 7 days)
1.
Query subject regarding any changes in general health and the use of concomitant 
medications.
2.
Record assessment of nasal cavity.  
3.
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. Also record concomitant medications/therapies used to treat AEs.
4.
Complete NOSE score assessment and VAS pain score.
5.
Instruct the subject on follow-up procedures, including returning the treatment facility 
at 42 days post-operative (± 7) days for follow-up visit.
6.
If applicable, complete an End of Study CRF.
End if Study (Visit 5) Day 42 (± 7 days)
1.
Query subject regarding any changes in general health and the use of concomitant 
medications.
2.
Record assessment of nasal cavity.  

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 51 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
3.
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. Also 
record concomitant medications/therapies used to treat AEs.
4.
Complete NOSE score assessment and VAS pain score.
5.
Complete an End of Study CRF.
Subjects may be provided participant stipends as agreed upon by Sponsor and the site, and as 
allowed by the site’s standard operating procedures/regulations and IRB. Stipend amounts may 
cover costs associated with the study participant to complete follow-up visits, but cannot be 
coercive.
Concomitant Medications and Therapies
Concomitant medications and concomitant procedures are recorded at any time from enrollment 
into the study through the subject’s last study visit. 
Any concomitant medications/ procedures associated with an AE, SAE or SADE will be 
recorded. 
Discontinued Subjects
Discontinued subjects are those who voluntarily discontinue participation, who are withdrawn for 
reasons of safety, who are lost to follow-up, or who have missed 2 study visits. Where possible, 
a full End of Study 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 7.9).
Finally, if appropriate, the Investigator will also advise the subject of subsequent therapy and/or 
procedures necessary for their medical condition. Medical care will not be provided to the 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 52 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
subject after the clinical investigation is completed, other than the standard care provided by the 
site, which is not considered a study visit(s).  
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 and a decision will be made regarding the continuation in the 
study of the pregnant woman. Pregnancy is not an adverse event; however, complications 
related to the pregnancy may be reportable as determined on a case-by-case basis. 
STUDY METHODS AND MEASUREMENTS
Nasal Obstruction Symptom Evaluation (NOSE) scale
The Nasal Obstruction Symptom Evaluation (NOSE)16,21 scale is a patient reported outcome 
(PRO) instrument that will be administered to capture subject perception of the degree of nasal 
airway patency. The Nose Scale will be completed at Screening, Day 5, Day 21 and Day 42.
The NOSE scale is a validated instrument, which was developed by the American Academy of 
Otolaryngology—Head and Neck Surgery (AAO-HNS) 16,21, and has been used in several clinical 
trials. The scale is brief, easy to complete, and is an important tool for pre- and post-intervention 
evaluation of symptoms in subjects with nasal obstruction. The NOSE Scale21 allows subjects to 
quantify their symptoms based on the severity of obstruction.
Subjects will be asked, “Since your last follow up visit, how much of a problem were the following 
conditions for you?” Specifically, subjects will be asked to rate their perceptions on the Likert 
scale with respect to the following characteristics:
o
Nasal congestion or stuffiness
o
Nasal blockage or obstruction

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 53 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
o
Trouble breathing through my nose
o
Trouble sleeping
o
Unable to get enough air through my nose during exercise or exertion
Participants will rate their responses using a Likert scale with response options 0, 1, 2, 3 or 4, as 
follows:
(0) Not a Problem
(1) Very Mild Problem
(2) Moderate Problem
(3) Fairly Bad Problem
(4) Severe Problem
Visual Analog Scale
A Visual Analog Scale (VAS)18 is a patient-reported outcome instrument that will be used to 
capture subjects’ degree of pain and in the area where ENTACT resorbable staples were 
implanted. The Visual Analog Scale (VAS) for pain is a continuous scale completed by the 
subject who is asked to place a line perpendicular to the VAS line at the point that represents 
their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on 
the 10-cm line between the “no pain” anchor and the subject's mark, providing a range of scores 
from 0–100. For pain intensity, the scale is most commonly anchored by “no pain” (score of 0) 
and “pain as bad as it could be” or “worst imaginable pain” (score of 100 [100-mm scale]). The 
VAS will be completed at Screening, Day 5, Day 21, and Day 42.
STATISTICAL DESIGN
A Statistical Analysis Plan (SAP) will be written and finalized prior to database lock. The SAP will 
contain more specific details of the statistical analyses that will be carried out as well as provide 
information on any changes or deviations from the projected analyses in this protocol. The 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 54 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Clinical Study Report (CSR) will also highlight changes made to the analyses specified in the 
protocol.
GENERAL
Smith+Nephew’s Global Biostatistics group or designee will conduct the statistical analysis for 
this study. Unless otherwise stated, all significance tests will be two-sided, performed at the 5% 
significance level. Resulting p-values will be quoted. Point estimates and their corresponding 
95% two-sided confidence intervals will be generated where appropriate. Where data summaries 
are specified, categorical and ordinal variables will be summarized with frequencies and 
percentages. Continuous variables will be summarized with the following summary statistics: 
number of observations, mean, median, standard deviation, minimum, and maximum values. All 
analyses will be performed in SAS 9.4 (or later).
ANALYSIS POPULATIONS
The following analysis populations will be used for this study:

Safety population (SAF): This includes all patients who have received the study 
device.

Full Analysis Set (FAS): This includes all patients who were recruited into the study 
and have at least one post-baseline visit.

Per-Protocol (PP) population: This includes all subjects in the FAS who have no 
significant protocol deviations and who meet all the inclusion/exclusion criteria.
Statistical analysis will be performed using each of the patient populations as follows: Analysis of 
the primary and secondary endpoints will be performed separately using both the FAS and PP 
populations. All safety analyses will utilize the SAF population. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 55 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
BASELINE DATA
Data to be summarized at baseline includes but is not limited to all collected demographic variable 
such as age, gender, primary diagnosis, height, weight, Body-Mass-Index and medical history. 
The baseline variables will be used to describe the outcome data where necessary.   
EFFICACY ANALYSIS
Analysis of Primary Endpoint
Data will be collected on whether the septum wall appearance and need for re-intervention at 
the surgery site are due to the device or the procedure. Only those that are device-related will 
contribute to the primary endpoint analyses, in line with the primary objective of this study.  A
binary variable will be defined as follows; one if all five of the following criteria are true and 0 if at 
least one of the criteria is false:

Septum wall straight appearance

Complete coaptation of perichondrial flaps on septum wall

Absence of significant local tissue reaction at the staple site

Absence of hematoma swelling at the staple site

No need for re-intervention at the surgery site
Clinical success will be inferred for a patient if their binary variable is 1. Clinical success will be 
reported as a count and percentage with a 95% CI using Clopper-Pearson Exact methodology. 
A logistic model will be used to evaluate the adjusted and unadjusted models for the primary 
outcome variable. The variables considered important and to be included in the final model are 
age and BMI. All other baseline and medical factors collected at baseline will be evaluated for 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 56 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
importance in adjusted models and only those statistically significant in an unadjusted model will 
be considered in the final model.
This analysis will be carried out using the FAS as the primary analysis population and the PP 
population using for sensitivity analysis.
Analysis of Secondary Endpoints
Nasal cavity assessments at day 5 and day 42 will be summarized and presented as count and 
percentage of each criterion. 
Successful staple deployment at the operative visit will be summarized by count and percentage. 
A 95% exact confidence interval for a single proportion will be presented for successful staple 
deployment using the Clopper-Pearson method. The number of staples used and whether the 
stapler misfired will also be presented. 
Total operating room time will be calculated and summarized using descriptive statistics and will 
be presented descriptively by septoplasty only cases as well as septoplasty and turbinate 
reduction cases. 
Intra-operative time to deploy staples to complete septoplasty, calculated as time between start 
of closure to when the stapler was handed back to the scrub nurse, will be summarized and 
presented descriptively by septoplasty only cases as well as septoplasty and turbinate reduction 
cases.
NOSE score will be calculated and summary statistics will be presented by visit. Change in 
NOSE score from the pre-operative visit to each post-operative visit will also be presented and 
an ANOVA model will be used to assess statistical significance. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 57 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
The VAS Pain score will be summarized by visit. Change in VAS Pain score from the pre-
operative visit to each post-operative visit will also be presented and an ANOVA model will be 
used to assess statistical significance. 
Analysis of Other Endpoints

Number and type of other S+N devices that are used with the turbinate reduction adjunct 
procedure.
SAFETY ANALYSES
All safety endpoints will be summarized using the safety population.
Adverse Events
The number of subjects reporting: adverse events, serious adverse events, severe adverse 
events, device-related adverse events, serious device-related adverse events, unanticipated 
adverse events, and serious unanticipated adverse events will be summarized. In addition, for 
each adverse event, the following will be summarized: severity, the relationship to the 
investigational device, outcome and duration of the resolved adverse events and the duration of 
the adverse events at trial discontinuation.
Device deficiencies
The number of device deficiencies and the number of patients reporting a device deficiency will 
be summarised.
Additional summaries of safety endpoints, if applicable, will be described in the SAP.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 58 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
INTERIM ANALYSES
There are no formal interim analyses planned for this study, however Clinical Activity Reports 
(CAR) may be produced to faciliate the publication of the results for scientific conferences and 
publications. Additional adhoc analyses may occur as needed (e.g. for abstracts or publications). 
SAMPLE SIZE JUSTIFICATION
The results of a previous clinical study17 on an earlier generation of the study device found that 
92% of subjects had successful fixation of tissue after one week. It is assumed that the study 
device will perform at least as well as the 92% found previously. The ICH E9 guidance states 
that power should be greater than or equal to 80%.24 Therefore based on statistical precision, 
the recruitment of 36 subjects would provide us with at least 80% probability of obtaining a 2-
sided 95% confidence interval, around the estimate proportion of successful fixations of tissue, 
to within ±11% precision. 
With the same assumption of clinical success rate and same precision target, enrolling 36
subjects in ENTACT (Next Generation) will provide probabilities between 78.4% and 90.3% of 
obtaining the 2-sided 95% confidence interval of the success rate. To allow for a 10% drop out 
rate, this study will enrol 40 subjects.
ADVERSE EVENTS AND DEVICE DEFICIENCIES
DEFINITIONS
The categories of adverse events are shown in table 12.1-1. The definitions for each of these 
categories are given in the subsequent sections.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 59 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Table 12.1-1: Categories of Adverse Event
NOT DEVICE-
RELATED
DEVICE- OR PROCEDURE-RELATED
NON-
SERIOUS
ADVERSE EVENT 
(AE)
ADVERSE DEVICE EFFECT 
(ADE)
SERIOUS
SERIOUS ADVERSE 
EVENT 
(SAE)
SERIOUS ADVERSE DEVICE EFFECT
(SADE) (SEE 12.1.3)
ANTICIPATED
UNANTICIPATED
ANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECT 
(ASADE)
UNANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECT  
(USADE)
Adverse Event
An Adverse Event (AE) is any untoward medical occurrence, unintended disease of untoward
clinical sign (including abnormal laboratory findings) in subjects, users or other persons, whether 
or not causally related to the IP/Ancillary Product.
Note 1: This definition includes events related to the IP, comparator or ancillary products. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to the IP
AE is used both to refer to AE which do not meet the definitions of Adverse Device Effects or 
Serious Adverse Events and as an umbrella term referring to adverse events of all 
classifications. 
An AE can be any unfavorable and unintended sign (for example, an abnormal laboratory 
finding), symptom, or disease. For reporting purposes, emphasis is placed first and foremost on 
whether or not the event constitutes an untoward medical occurrence. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
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Version: 2.0, 27Aug2020
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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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Adverse Device Effect
An Adverse Device Effect (ADE) is an adverse event that, in the opinion of the investigator, is 
related to the use of the IP. 
Note 1: 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: This definition includes any event resulting from use error or from intentional misuse 
of the investigational 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 or UNLIKELY 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, PROBABLE, 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.
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, in the view of either the Investigator or the Sponsor, it:

a) led to death,

b) led to serious deterioration in the health of the subject, that either resulted in
o
1) a life-threatening illness or injury, or

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
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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 
is contrary to the expressed or implied wishes of Smith + Nephew. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
o
2) a permanent impairment of a body structure or a body function, or
o
3) in-patient or prolonged hospitalization, or
o
4) medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body function,

c) led to foetal distress, foetal death or a congenital abnormality or birth defect
Note: 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.
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 analysis 
report. 
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report (see Section 4.4 for 
details).
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:
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 
enough to cause interference with the subject’s usual activities;

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
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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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Severe -  
An event is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities.
Device Deficiency
A Device Deficiency (DD) 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. 
AE CODING DICTIONARY 
Coding for this study will be done per International Medical Device Regulators Forum (IMDRF) 
AE Terminology Annex E – Clinical signs, symptoms, and conditions
REPORTING PROCEDURES
AE of any kind and DD will be recorded in the applicable CRF and source notes. The 
Investigator will evaluate all AE for relationship to the device and procedure, if applicable, 
seriousness, and severity. 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 12.3-1 and Figure 12.3-2):

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)
For ADE and DD, 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 the timescales above.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 63 of 94 
 
 
 
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 
is contrary to the expressed or implied wishes of Smith + Nephew.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
All adverse events 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 IRB/ Independent Ethics Committee (IEC) of adverse events 
according to the IRB/IEC requirements.  
Depending on the nature of the adverse event, S+N may request copies of the subject’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 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 Investigator Site File (ISF) Sponsor Contact 
Information Sheet to report SAE, unanticipated ADE and SADE, anticipated SADE, and DD. 
 
 
 
 
 
 
 
 
 
 
 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 64 of 94 
 
 
 
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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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
Figure 12.3-1: Evaluation and Reporting of AE 
Site 
aware 
of AE
Investigator 
assesses 
seriousness 
Serious
Investigator 
assesses device 
relationship
Related 
Investigator 
assesses whether 
SADE is 
anticipated
Not Related
Serious Adverse 
Event (SAE)
unanticipated
Unanticpated 
Serious Adverse 
Device Effect 
(USADE)
Anticipated 
Serious Adverse 
Device Effect 
(ASADE)
Investigator 
assesses device 
relationship
Non-serious
Related
Adverse Device 
Effect (ADE)
Not Related
Adverse Event 
(AE)
Complete CRF 
and alert S&N 
IMMEDIATELY  
Record 
information in 
patient CRF 
according to 
usual 
timescales.
Complete CRF 
and alert S&N 
without 
unreasonable 
delay. 
Record 
details in 
subject s 
medical 
records
 
 
 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
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Version: 2.0, 27Aug2020
Page: Page 65 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Figure 12.3-2: Evaluation and Reporting of Device Deficiencies
Site aware 
of DD
Investigator 
assesses whether 
could have led to 
SADE 
Potential to cause SADE
No potential to cause SADE
Complete CRF and alert S&N 
IMMEDIATELY  
Record information in patient 
CRF according to usual 
timescales.
Record details in subject s 
medical records
UNBLINDING OF INVESTIGATIONAL PRODUCT
Not Applicable
FOLLOW-UP OF SUBJECTS WITH ADVERSE EVENTS
For subjects who are experiencing ongoing unresolved AE at the time of their study completion 
or early discontinuation from the study, it is recommended that the Investigator schedule an 
appropriate follow-up visit to determine the outcome of the event. 
Any additional data must be documented and available to the Sponsor, who will determine 
whether the data need to be documented in the CRF, and as required, the Clinical Study Report.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
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Version: 2.0, 27Aug2020
Page: Page 66 of 94
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 
is contrary to the expressed or implied wishes of Smith + Nephew. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Ongoing Adverse Events at Study Discontinuation
Adverse events which are related to a study procedure or S&N IP and are ongoing at the end of 
subject’s participation: The event should be followed until it is either resolved or until the event 
has become chronic and is not expected to further improve based on Investigator’s review of the 
event.
Adverse events which are not related to a study procedure or S&N IP and are ongoing at the
end of subject’s participation should be followed for 30 days after discontinuation or if 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.
INVESTIGATOR OBLIGATIONS
The Principal Investigator will comply with the commitments outlined in the Statement of 
Investigator, provided by the Sponsor, and with Good Clinical Practice (GCP) and all applicable 
regulatory requirements as outlined in Appendix 21.5 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.
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 the 
source documents; and the study is conducted in compliance with the currently approved 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 67 of 94
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 
is contrary to the expressed or implied wishes of Smith + Nephew. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
protocol and amendment(s), if applicable, with GCP regulations, and with applicable regulatory 
requirements.
Detailed monitoring requirements will be documented in the Clinical Monitoring Plan for this 
study. 
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.
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. 
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. 
CLOSE-OUT VISIT
A study close-out visit 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 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
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Version: 2.0, 27Aug2020
Page: Page 68 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
requirements regarding records retention and IRB/IEC reporting requirements. When no 
subjects have been included, a remove close-out visit may be conducted. 
PROTOCOL AMENDMENTS
Amendments should be made only in necessary 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.
CONFIDENTIALITY OF THE STUDY
The confidentiality of this study and associated documents is governed by the terms of the 
Clinical Trial Agreement (CTA).
STATEMENTS OF COMPLIANCE
The investigation was conducted in compliance with applicable requirements in the protection of 
human subjects’ regulations in 21 CFR part 50, Good Clinical Practices, the institutional review 
board’s regulations in 21 CFR part 56. In compliance with the Food and Drug Administration 
Amendments Act of 2007 (FDAAA), this study will be listed in www.clinicaltrials.gov.  
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 Practice20, 22.
This clinical study will not commence until the required approval/favorable opinion from the IRB
or regulatory authority has been obtained. Any additional requirements imposed by the IRB or 
regulatory authority will be followed. 
Public/Products 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 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
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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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
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.
END OF STUDY
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. 
The end of study CRF needs to be completed for any subject that does not complete the study, 
to document the reason for termination.
The entire study may be terminated if deemed necessary by the Sponsor (e.g. the product is 
determined to not be safe). Sites may be terminated for reasons that include, but are not limited 
to non-compliance to the protocol, ethical violations, or inability to recruit subjects. 
PUBLICATION POLICY
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, including, but not limited to the Health Insurance 
Portability and Accountability Act of 1996.
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 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
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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-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
The International Committee of Medical Journal Editors (ICMJE) published on the 6th June 
201726. 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 nine 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 the sponsor. To gain access, data requestors will need to sign a data access 
agreement. 
 
 
 
 
 
 
 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 71 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
REFERENCES
1. Barrett DM, Casanueva FJ, Cook TA. Management of the Nasal Valve. Facial Plast Surg 
Clin North Am. 2016;24(3):219-234.
2. Kim JS, Kwon SH. Is nonabsorbable nasal packing after septoplasty essential? A meta-
analysis. The Laryngoscope. 2017;127(5):1026-1031.
3. Mane RS, Patil B, Mohite A. Comparison of septoplasty with and without nasal packing 
and review of literature. Indian journal of otolaryngology and head and neck surgery: 
official publication of the Association of Otolaryngologists of India. 2013;65(Suppl 2):406-
408.
4. Wang WW, Dong BC. Comparison on effectiveness of trans-septal suturing versus nasal 
packing after septoplasty: a systematic review and meta-analysis. European archives of 
oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-
Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino-
Laryngology - Head and Neck Surgery. 2017;274(11):3915-3925.
5. Sowerby LJ, Wright ED. A comparison of septal stapler to suture closure in septoplasty: 
a prospective, randomized trial evaluating the effect on operative time. International 
forum of allergy & rhinology. 2013;3(11):911-914.
6. Banglawala SM, Gill MS, Dhillion N, et al. Nasal packing after septoplasty: 
Cardiopulmonary impact. JAMA Otolaryngology - Head and Neck Surgery. 
2014;140(3):253-258.
7. Certal V, Silva H, Santos T, Correia A, Carvalho C. Trans-septal suturing technique in 
septoplasty: a systematic review and meta-analysis. Rhinology. 2012;50(3):236-245.
8. Yildirim G, Cingi C, Kaya E. Septal stapler use during septum surgery. European 
archives of oto- rhino-laryngology : official journal of the European Federation of Oto-
Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-
Rhino-Laryngology - Head and Neck Surgery. 2013;270(3):939-943.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 72 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
9. Fujiwara T, Kuriyama A, Kato Y, Fukuoka T, Ota E. Perioperative local anaesthesia for 
reducing pain following septal surgery. The Cochrane database of systematic reviews. 
2018;8:Cd012047. 
10. Quinn JG, Bonaparte JP, Kilty SJ. Postoperative management in the prevention of 
complications after septoplasty: a systematic review. The Laryngoscope. 
2013;123(6):1328-1333. 
11. Kuppersmith RB, Atkins JH, Tami TA. The use of bioresorbable staples for 
mucoperichondrial flap coaptation in septoplasty. Otolaryngology--head and neck surgery 
: official journal of American Academy of Otolaryngology-Head and Neck Surgery. 
2009;140(4):599-600. 
12. Sainio S, Blomgren K, Lundberg M. Complications and number of follow-up visits after 
using septal stapler in septoplasty. Rhinology. 2019. 
13. Tami TA, Kuppersmith RB, Atkins J. A clinical evaluation of bioresorbable staples for 
mucoperichondrial flap coaptation in septoplasty. American journal of rhinology & allergy. 
2010;24(2):137 139. 
14. IFU. 55675 Rev F, ENTACT Septal Stapler (Previous Generation). 
15. IFU. 73051.EN Rev D ENTACT Septal Stapler (Next Generation)). 
16. Stewart, M. G., D. L. Witsell, T. L. Smith, E. M. Weaver, B. Yueh and M. T. Hannley 
(2004). "Development and validation of the Nasal Obstruction Symptom Evaluation 
(NOSE) scale." Otolaryngol Head Neck Surg 2004;130: 157-163.  
17. ClinicalTrials.gov. NIH National Library of Medicine (U.S)(March 2012) Comparison of a 
Septal Stapler to Suture Closure in Nasal Septoplasty Identifier NCT01541839 retrieved 
from: https://clinicaltrials.gov/ct2/show/NCT01541839. 
18.  Streiner DL,Norman GR. Health measurement scales: a practical guide to their 
development and use. New York; Oxford University Press,1989. 
19. Clark, D. W., Del Signore, A. G., Raithatha, R., & Senior, B. A. (2018). Nasal Airway 
Obstruction: Prevalence and Anatomic Contributors. Ear, Nose & Throat Journal, 97(6), 
173–176. https://doi.org/10.1177/014556131809700615. 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 73 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
20. International Organization for Standardization. ISO14155:2011 Clinical Investigation of 
Medical Devices for Human Subjects -- Good Clinical Practice (Edition 2). 2nd ed.; 2011. 
21. Nasal Obstruction Symptom Evaluation (NOSE) Instrument. nt. 
https://www.entnet.org/content/facial-plasticsrhinology-outcome-tool-nose-scale 
22. International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
For Human Use (ICH). Integrated Addendum to ICH E6(R1): Guideline for Good Clinical 
Practice E6(R2). Vol Step 4; 2016.Taichman, DB, et al. Data Sharing Statements for 
Clinical Trials: A Requirement of the International Committee of Medical Journal Editors. 
Ann Intern Med. 2017. 6th June. doi:10.7326/M17-1028 
23. ICH Topic E9. Guidance document Statistical principles for clinical trials 2018, page 22 
https://www.fda.gov/media/71336/downlo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 74 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
APPENDICES
PROTOCOL AMENDMENT 
General Purpose
It was requested by the notified body TUV, which stands for (Technischer Überwachungsverein, 
English translation: Technical Inspection Association), to update the protocol based on the 
feedback provided by the TUV reviewer. The following amendments were made to correct and 
clarify the protocol. This study will start subject enrollment with Protocol Version 2.0.
Rationale
The rationale for the changes are as follows:
Rationale 1: Per the TUV review, the inclusion criteria are stricter than those mentioned 
in the IFU (e.g., age 18 and older). Removed age inclusion to allow the standard of care 
data to be collected for this study per the recommendations of the TUV. In 
addition, Section 7.5 was updated to include vulnerable populations and minors 
informed consent language.
Rationale 2: Per the TUV review, the exclusion criteria exceeded those in the IFU (e.g., 
diabetes, pregnancy, previous septoplasty, smokers, etc.). Removed diabetes, previous 
septoplasty, and smokers as an exclusion criteria to allow the standard of care data to be 
collected for this study per the recommendations of the TUV. Clarification provided 
regarding pregnancy to pregnant at time of procedure.  Pregnant women, fetuses, and 
neonates are often considered vulnerable and protected by ISO and additional
regulations. Any elective surgeries such as a septoplasty are off-limits during pregnancy. 
Although work done to the nose has nothing to do with the womb, the sedation and 
medication will be harmful to the growing fetus. Subjects are allowed to continue 
participation in the trial if they do become pregnant after the procedure. The additional 
tests included in the study schematic do not pose a risk to the subject or the fetus.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 75 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
Rationale 3: TUV requested further clarification regarding the sample size. As the sample 
size was not clear, explaining why an 80% power confidence is acceptable. Per ICH, E9 
guidance states that power should be greater than or equal to 80%. 80% is a widely used 
industry standard. Thirty-six subjects would provide us with at least 80% probability of 
obtaining a 2-sided 95% confidence interval, around the estimate proportion of 
successful fixations, to within ±11% precision. To allow for a 10% drop out rate, this 
study will enroll 40 subjects.
Rationale 4: TUV expressed concerns regarding the potential bias of the surgeon with 
follow up exams. Therefore a statement was added in Section 8.4.3; the follow-up 
exams will be delegated by the Investigators not involved in the procedure to reduce 
potential bias by the surgeon.
Rationale 5: Sections 4.2, 4.2.2, and 4.4.1 were added and updated to provide ENTACT 
staple system safety data collected from literature. Tolerance limits for potential adverse 
effects were derived from Section 4.2.2.
Rationale 6: Administrative changes, removing duplicate words, and adding citations.
Effect on Study Status
Not applicable; this amendment is to be in effect and implemented prior to subject enrollment
Details
Section
Heading
Current Text 24/APR/2020 
Version 1.0 
Version 1.0, Date 24Apr2020 
original protocol
Revised Text 27/AUG/2020 Version 2.0
Version 2.0  Date 27Aug2020
1.1 Protocol 
Signature 
Page
I have read the attached 
protocol entitled “A prospective, 
multi-center, single arm PMCF 
study to evaluate the safety and 
performance of ENTACT™
(Next Generation) resorbable 
I have read the attached protocol entitled “A prospective, multi-
center, single arm PMCF study to evaluate the safety and 
performance of ENTACT™(Next Generation) resorbable septal 
staple system for septoplasty”, version 2.0, dated 27Aug2020 , 
and agree to abide by all provisions set forth herein.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 76 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
septal staple system for 
septoplasty”, version 1.0, dated 
24Apr2020, and agree to abide 
by all provisions set forth 
herein. 
I agree to comply with the 
Investigator’s Obligations 
stipulated in Section 21.2 of the 
protocol,  
 
I agree to comply with the Investigator’s Obligations stipulated in 
Section 21.5 of the protocol,  
 
1.2 
Coordinating 
Investigator 
Approval 
I have read the attached 
protocol entitled “A prospective, 
multi-center, single arm PMCF 
study to evaluate the safety and 
performance of ENTACT™ 
(Next Generation) resorbable 
septal staple system for 
septoplasty”, version 1.0, dated 
24Apr2020, and agree to abide 
by all provisions set forth 
therein. 
I have read the attached protocol entitled “A prospective, multi-
center, single arm PMCF study to evaluate the safety and 
performance of ENTACT™ (Next Generation) resorbable septal 
staple system for septoplasty”, version 2.0, dated 27Aug2020 , 
and agree to abide by all provisions set forth therein. 
 
 
1.3 Sponsor 
Approval 
Head of Global 
Biostatistics 
Head of Global Data Analytics 
2. Synopsis  
Sample size 
Minimum of 30 and maximum of 
40 subjects 
 
The results of a previous clinical 
study on previous generations 
of the study device found that 
92% of subjects had successful 
fixation of tissue after one week. 
It is assumed that the study 
device will perform at least as 
well as the 92% found 
previously. Therefore based on 
statistical precision, the 
recruitment of 36 subjects 
would provide with at least 80% 
probability of obtaining a 2-
sided 95% confidence interval, 
around the estimate proportion 
of successful fixations of tissue, 
to within ±11% precision. 
 
40 subjects  
The results of a previous clinical study on previous generations of 
the study device found that 92% of subjects had successful 
fixation of tissue after one week. It is assumed that the study 
device will perform at least as well as the 92% found previously. 
Therefore based on statistical precision, the recruitment of 36 
subjects would provide with at least 80% probability of obtaining a 
2-sided 95% confidence interval, around the estimate proportion 
of successful fixations of tissue, to within ±11% precision.  
With the same assumption of clinical success rate and same 
precision target, enrolling 36 subjects in ENTACT, Next 
Generation will provide probabilities between 78.4% and 90.3% of 
obtaining the 2-sided 95% confidence interval of the success rate. 
To allow for a 10% drop out rate, this study will enrol 40 subjects. 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 77 of 94 
 
 
 
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 
is contrary to the expressed or implied wishes of Smith + Nephew.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
The study will aim to enroll a 
minimum of 30 subjects and a 
maximum of 40 subjects. With 
the same assumption of clinical 
success rate and same 
precision target, enrolling 
between 30 and 40 subjects in 
ENTACT Next Generation will 
provide probabilities between 
78.4% 
and 90.3% of obtaining the 2-
sided 95% confidence interval 
of the success rate. 
2. Synopsis  
Inclusion 
criteria 
The patient will be eligible for 
the study if he or she meets all 
of the 
following inclusion criteria at the 
baseline screening: 
1. Able and willing to give 
informed consent by voluntarily 
providing written informed 
consent in accordance with 
governing Institutional Review 
Board (IRB); 
2. Male or female, aged 18 
years and older with a clinically 
significant deviation of the nasal 
septum; 
3. Willing and able to make all 
required study visits; 
4. Able to read and understand 
the approved informed consent 
form and patient reported 
outcome assessments (written 
and 
oral). 
The patient will be eligible for the study if he or she meets all of 
the following inclusion criteria at the baseline screening: 
1. Able and willing to give informed consent by voluntarily 
providing written informed consent in accordance with 
governing Institutional Review Board (IRB); 
2. Clinically significant deviation of the nasal septum; 
3. Willing and able to make all required study visits; 
4. Able to read and understand the approved informed 
consent form and patient reported outcome assessments 
(written and oral). 
2. Synopsis 
Exclusion 
Criteria 
The patient will be ineligible for 
the study if he or she meets any 
of the following exclusion 
criteria at the baseline 
screening or during surgery: 
1. Prolonged tissue 
approximation beyond 
that needed for normal 
The patient will be ineligible for the study if he or she meets any of 
the following exclusion criteria at the baseline screening or during 
surgery: 
1. Prolonged tissue approximation beyond that needed for 
normal tissue closure is necessary or desired; 
2. Traditional suturing techniques is necessary;  
3. Radiopacity is necessary or desired since ENTACT septal 
staples are radiotransparent; 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 78 of 94 
 
 
 
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 
is contrary to the expressed or implied wishes of Smith + Nephew.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
tissue closure is 
necessary or desired;  
2. Traditional suturing 
techniques is 
necessary; 
3. Radiopacity is 
necessary or desired 
since ENTACT septal 
staples are 
radiotransparent; 
4. Known to be allergic to 
foreign body of 
materials of 
investigational product; 
5. Concomitant 
procedures other than 
turbinectomy, turbinate 
reduction, and/or sinus 
surgery; 
5. Uncontrolled diabetes; 
6. Pregnancy; 
7. Previous septoplasty; 
8. Presence of infection at 
the site; 
9. Smokers and severe 
drug and alcohol 
abusers; 
10. Autoimmune disease 
deemed clinically 
significant by Principal 
Investigator (PI). 
4. Known to be allergic to foreign body of materials of 
investigational product; 
5. Concomitant procedures other than turbinectomy, 
turbinate reduction, and/or sinus surgery; 
6. Pregnancy at time of procedure; 
7. Presence of infection at the site; 
8. Severe drug and alcohol abusers; 
9. Autoimmune disease deemed clinically significant by 
Principal Investigator (PI). 
3.  Table of 
Contents 
and through 
protocol 
Original sections and page 
numbers  
 
Updated sections and page numbers  
 
4.2 
Literature 
summary 
 
This section aims to provide a “state of the art” review for the 
indications in which ENTACT (Next Generation) resorbable septal 
staple system is intended to be used per Section 4.4. A literature 
search was conducted to identify recently published articles on 
septoplasty. 
Limitations such as language or article type were imposed in 
some searches for publications. Limiting searches to systematic 
reviews, and meta-analysis was performed to obtain integrated 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 79 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
findings from several selected studies considered to be 
supportive of evidence-based practices. The results of these 
studies are discussed in terms of their general conclusions. 
This report aims to identify clinical studies or usage of the current 
Smith & Nephew ENTACT Septal Stapler through an extensive 
literature search.  
In the current evaluation, the PubMed online database (MedLine 
component) and Embase was used to find clinical results. The 
medical literature was searched for an unrestricted period of time 
through July 2019. The search was performed by a qualified 
Evidence Evaluation Specialist, in July, 2019. 
4.2.2 Safety   
Complications identified in the four clinical publications are 
reported in Table 4.2.2 -1. 
 Table 4.2.2-1. ENTACT Septal Stapler Complications 
 
 
 
 
 
 
 
 
Device related complications were reported in three studies.5,13,12 
Perforation was reported in two studies.5,12 Sainio et al.12  reported 
perforation in 1 patient (0.99%) in the ENTACT Stapler group and 
a reoperation was performed in this patient. Sowerby et al.5 
reported a 1 mm postoperative perforation occurred in one patient 
(12.5%) due to jamming of the ENTACT Septal Stapler (2009) and 
stated that this can be avoided with the newer model (2010/2012) 
of the stapler. Perforation was in line with other outcomes reported 
in the State of the Art for alternative devices for the Sainio12 study. 
In Sowerby et al.5, the authors concluded that the septal stapler 
can be used without an increased morbidity in comparison to 
suture closure or impact to subjective patient scores.   
 
Tami et al13 reported that the first lot of ENTACT Septal Staplers 
(2009) failed to perform to design specifications and only four total 
staples from three staplers were implanted in one patient.  
 
Sainio et al.12 observed haematoma in one patient in the ENTACT 
Stapler group. Sainio et al.12 reported that perforation and 
haematoma, which occurred at a low rate of 1% each in the study, 
is in agreement with the study conducted by Tami et al.13 and 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 80 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
stated that “ENTACT Septal Stapler is safe to use”.  The 
complications reported in the four studies of the ENTACT stapler 
are performing in-line with alternative devices on the market as 
discussed in the State of the Art.  
 
Some of the minor complications observed in the literature were 
edema, inflammation and infection. Sowerby et al.5 conducted a 
prospective, randomized clinical study comparing ENTACT Septal 
Stapler to quilting sutures in patients undergoing septoplasty. 
Sowerby et al.5 observed mild edema in 2 patients in both the 
groups at a 3 week follow up. However, the edema resolved in 2 
months. In a prospective, case series13, mild inflammation was 
reported at a 1 week follow up in 21% of the patients in whom 
ENTACT Septal Stapler was used for approximation of 
mucoperichondrial flaps after septoplasty whereas no 
inflammation was observed in 79% of the patients. Expected rates 
of edema or inflammation following septoplasty were not 
discussed in the four publications identified. Other complications 
reported in the literature include bleeding,12 and fever.12  
 
Sainio et al.12 conducted a retrospective comparative study 
comparing ENTACT Septal Stapler to the non-stapler group where 
silicone splints, tamponade, or sutures were used during 
septoplasty. No significant difference in the complication rate was 
observed between the ENTACT Septal Stapler group (9.9%) and 
the subgroups such as silicone splint group (9.7%), suture group 
(12.7%), and the tamponade group (9.5%) in the non-stapler 
group.12 
 
Since the ENTACT (Next Generation) Septal Stapler utilizes the 
same staples and a similar delivery mechanism to the previous 
ENTACT Septal Stapler, it is anticipated that the Next Generation 
device will perform the same as the previous generation device. 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 81 of 94 
 
 
 
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 
is contrary to the expressed or implied wishes of Smith + Nephew.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
4.4.1 
Tolerance 
limits for 
potential 
adverse 
effects 
derived 
from 
literature 
 
 
Based on the state of the art data in Table 4.2.2-1 and Section 
4.2.2  the expected tolerance limits for potential adverse effects 
from literature in the ENTACT Septal Stapler are the stated in 
Table 4.4.1-1 
 
Actual study adverse events occurrences will be reviewed under 
Section 10.5 and Section 12 and assessed relative to the 
tolerance limits.  
5.4 Claims 
 
Increased distance 
between both the distal 
ends for 
accommodating 
broader range of 
anatomies; 
 
Overall, approximately 
30% reduction in the 
distal arm volume for 
improved posterior 
access. 
Removed claims- data not collected in this study  
7.1 Subject 
Population 
A minimum of 30 and maximum 
of 40 individuals to be 
approached for participation in 
this study and will include adult 
patients (ages 18 and over) who 
are receiving or seeking care for 
nasal septal obstructions. 
Subjects will be enrolled up to 3 
sites across the United States. 
Forty (40) individuals to be approached for participation in this 
study who are receiving or seeking care for nasal septal 
obstructions. Subjects will be enrolled up to 3 sites across the 
United States. 
7.2 
Inclusion 
Criteria 
1. Able and willing to give 
informed consent by 
voluntarily providing 
written informed consent 
in accordance with 
1. Able and willing to give informed consent by voluntarily 
providing written informed consent in accordance with 
governing Institutional Review Board (IRB); 
2. clinically significant deviation of the nasal septum; 
3. Willing and able to make all required study visits; 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 82 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
governing Institutional 
Review Board (IRB); 
2. Male or female, aged 18 
years and older with a 
clinically significant 
deviation of 
3. the nasal septum; 
4. Willing and able to make 
all required study visits; 
5. Able to read and 
understand the approved 
informed consent form 
and patient reported 
outcome assessments 
(written and oral). 
4. Able to read and understand the approved informed 
consent form and patient reported outcome assessments 
(written and oral). 
7.3 
Exclusion 
Criteria 
1. Prolonged tissue 
approximation beyond that 
needed for normal tissue 
closure is necessary or 
desired; 
2. Traditional suturing 
techniques is necessary; 
3. Radiopacity is necessary or 
desired since ENTACT 
septal staples are 
radiotransparent; 
4. Known to be allergic to 
foreign body of materials of 
investigational product; 
5. Concomitant procedures 
other than turbinectomy, 
turbinate reduction and/or 
sinus 
6. surgery; 
7. Uncontrolled diabetes; 
8. Pregnancy; 
9. Previous septoplasty; 
10. Presence of infection at the 
site; 
11. Smokers and severe drug 
and alcohol abusers; 
12. Autoimmune disease 
deemed clinically significant 
by Principal Investigator. 
1. Prolonged tissue approximation beyond that needed for 
normal tissue closure is necessary or desired; 
2. Traditional suturing techniques is necessary; 
3. Radiopacity is necessary or desired since ENTACT septal 
staples are radiotransparent; 
4. Known to be allergic to foreign body of materials of 
investigational product; 
5. Concomitant procedures other than turbinectomy, 
turbinate reduction and/or sinus surgery; 
6. Pregnancy at time of procedure; 
7. Presence of infection at the site; 
8. Severe drug and alcohol abusers; 
9. Autoimmune disease deemed clinically significant by 
Principal Investigator. 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 83 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
7.4 
Screening 
A minimum of 30 and a 
maximum of 40 individuals to be 
approached for participation. 
Subjects will be enrolled as they 
meet eligibility and consent to 
the study. 
40 individuals to be approached for participation. Subjects will be 
enrolled as they meet eligibility and consent to the study.   
7.5 Informed 
Consent  
Before conducting any study 
procedures or examinations, 
informed consent shall be 
obtained from all participants 
according to ISO14155 
guidelines. Patients must be 
informed as to the purpose of 
the study and the potential risks 
and benefits known or that can 
be reasonably predicted or 
expected as described in the 
written Informed Consent Form 
(ICF). The patients shall have 
sufficient opportunity to 
consider participation in the 
study. Patients will then be 
invited to read, sign and 
personally date the Institutional 
Review Board (IRB)-approved 
ICF, indicating their consent for 
enrollment. Additionally, the 
individual who obtains consent 
from the participant will sign and 
date the ICF. A copy of the 
signed informed consent 
documentation will be provided 
to the participant, and the 
original filed in the investigator 
site file (ISF). Once the subjects 
has consented, the PI or 
delegated. 
Before conducting any study procedures or examinations, 
informed consent shall be obtained from all participants according 
to ISO14155 guidelines the Health Insurance Portability and 
Accountability Act (HIPAA, if applicable), and local regulations. 
Patients must be informed as to the purpose of the study and the 
potential risks and benefits known or that can be reasonably 
predicted or expected as described in the written Informed 
Consent Form (ICF). The patients shall have sufficient opportunity 
to consider participation in the study. Patients will then be invited 
to read, sign and personally date the Institutional Review Board 
(IRB)-approved ICF, indicating their consent for enrollment. 
Additionally, the individual who obtains consent from the 
participant will sign and date the ICF. A copy of the signed 
informed consent documentation will be provided to the 
participant, and the original filed in the investigator site file (ISF). 
In the case of vulnerable subjects, the ICF must be understood 
and signed by the subject’s legally authorized representative 
(parent or legal guardian). Assent to participate in the study 
should be obtained for subjects ≥7 years of age and <18 years of 
age if allowed by local regulations. For subjects less than 7 years 
of age an assent will not be obtained. 
In the case of minors, the ICF must be obtained by their legally 
designated representative.  The minor shall participate in the 
informed consent process in a way suitable for his/her age and 
mental maturity. Minors will receive the study information in a way 
adapted to their age and mental maturity from investigators or 
members of the investigating team who are trained or experienced 
in working with children. If minors express a wish or an opinion 
with regards to study participation this needs to be respected by 
the Investigator. If during the study, the minor reaches the age of 
18 years (legal competence), the informed consent shall be 
obtained again, before the subject can continue to participate in 
the clinical investigation. 
8.1 Study 
Design 
This is a prospective, multi-
center, single arm PMCF study 
to evaluate the safety and 
This is a prospective, multi-center, single arm PMCF study to 
evaluate the safety and performance of the ENTACT (Next 
Generation) resorbable staple system for septoplasty in 40 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 84 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
performance of the ENTACT 
(Next Generation) resorbable 
staple system for septoplasty in 
a minimum of 30 and maximum 
of 40 subjects. The study 
purpose is to provide evidence 
to satisfy 
the PMCF requirements of CE 
Marking to market this device in 
Europe (data may be used to 
support registrations on other 
countries as well). 
subjects. The study purpose is to provide evidence to satisfy the 
PMCF requirements of CE Marking to market this device in 
Europe (data may be used to support registrations on other 
countries as well).   
8.3.3 Safety 
Endpoints 
 
Device-related re-
intervention; 
 
All adverse events 
(AEs) occurring from 
the time of surgery until 
re-interention or study 
completion; 
 
Device-related re-intervention; 
 
All adverse events (AEs) occurring from the time of 
surgery until re-intervention or study completion; 
 
8.4.2 
Screening of 
Subjects 
In order to eliminate selection 
bias, the Investigators will 
continuously screen all 
subjects. Subject recruitment 
continues until the completion of 
recruitment subject recruitment. 
In order to eliminate selection bias, the Investigators will 
continuously screen all subjects. Subject recruitment continues 
until the completion of subject recruitment. 
 
8.4.3 
Investigator 
Training 
Prior to the clinical trial, the 
clinical research associate 
(CRA), coordinating with the 
persons in charge of the study 
sites, will train the Investigators 
on the study protocol, making 
sure they are 
familiar with the use of 
investigational medical device, 
and implement subject 
enrollment strictly in accordance 
with the inclusion criteria and 
exclusion criteria, conduct 
relevant examinations 
according to the protocol 
requirements, also master all 
new device-related information 
found 
Prior to the clinical trial, the clinical research associate (CRA), 
coordinating with the persons in charge of the study sites, will train 
the Investigators on the study protocol, making sure they are 
familiar with the use of investigational medical device, and 
implement subject enrollment strictly in accordance with the 
inclusion criteria and exclusion criteria, conduct relevant 
examinations according to the protocol requirements, also master 
all new device-related information found during the clinical trial, 
thus to minimize the interferential factors. The follow-up exams will 
be delegated by the Investigators not involved in the procedure to 
reduce potential bias by the surgeon. 

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 85 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
during the clinical trial, thus to 
minimize the interferential 
factors.
11.0
Samples 
Size 
Justification
The results of a previous clinical 
study17 on an earlier 
generation of the study device 
found that 92% of subjects had 
successful fixation of tissue 
after one week. It is assumed 
that the study device will 
perform at least as well as the 
92% found previously. 
Therefore based on statistical 
precision, the recruitment of 36 
subjects would provide us with 
at least 80% probability of 
obtaining a 2-sided 95% 
confidence interval, around the 
estimate proportion of 
successful fixations of tissue, to 
within ±11% precision.
The study will aim to enrol a 
minimum of 30 subjects and a 
maximum of 40 subjects. With 
the same assumption of clinical 
success rate and same 
precision target, enrolling 
between 30 and 40 subjects in 
ENTACT (Next Generation) will 
provide probabilities between 
78.4% and 90.3% of obtaining 
the 2-sided 95% confidence 
interval of the success rate.
The results of a previous clinical study17 on an earlier generation 
of the study device found that 92% of subjects had successful 
fixation of tissue after one week. It is assumed that the study 
device will perform at least as well as the 92% found previously. 
The ICH E9 guidance states that power should be greater than or 
equal to 80%.24  Therefore based on statistical precision, the 
recruitment of 36 subjects would provide us with at least 80% 
probability of obtaining a 2-sided 95% confidence interval, around 
the estimate proportion of successful fixations of tissue, to within 
±11% precision. 
With the same assumption of clinical success rate and same 
precision target, enrolling 36 subjects in ENTACT (Next 
Generation) will provide probabilities between 78.4% and 90.3% 
of obtaining the 2-sided 95% confidence interval of the success 
rate. To allow for a 10% drop out rate, this study will enrol 40 
subjects.
20.0
References
Addition of references 20-23
Approval/Notification
It will be necessary to obtain IRB/EC approval prior to implementation of any change in the 
protocol that may affect the scientific soundness or the rights, safety, or welfare of the subjects 
involved. Notification shall be submitted to the IRB/EC of the study site by the Investigator.

Study Protocol
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty
Number:
ENTACT.ENT.PRO.SEP.2019.05
Version: 2.0, 27Aug2020
Page: Page 86 of 94
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. 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols
INSTRUCTIONS FOR USE
Refer to the Instruction for Use supplied with this protocol
EQUIPMENT AND SPECIAL INSTRUCTIONS
Not Applicable
ADDITIONAL INFORMATION
Not applicable
PRINCIPAL INVESTIGATOR OBLIGATIONS (ISO14155:2011)
1. General: 
a.
The role of the PI is to implement and manage 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. 
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 International 
Standard; evidence of such qualifications of the PI and key members of the 
investigation site team shall be provided to the Sponsor through up-to-date Curriculum 
Vitae (CV) or other relevant documentation,
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 interfere with the conduct 
of the clinical investigation or interpretation of results, and
d.
be knowledgeable with the method of obtaining informed consent.

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 87 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
3. Qualification of investigation site. The PI shall be able to demonstrate that the proposed 
investigation site: 
a. 
has the required number of eligible subjects needed within the agreed recruitment 
period, and 
b. 
has one or more qualified investigators, a qualified investigation site team and adequate 
facilities for the foreseen duration of the clinical investigation. 
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 IEC, 
b. 
comply with the requirements described in 4.5 of ISO 14155:2011. 
i. 
Submit to the IEC the following information, any amendments and any additional 
documentation required by the IEC: the Protocol; IB or equivalent; informed 
consent form and any other written information provided to subjects; procedures 
for recruiting subjects and advertising materials, if any; a copy of the CV of the 
PI(s) for with the IEC has oversight. 
ii. 
Provide documentation of the IECs approval/favorable opinion, identifying the 
documents and amendments on which the opinion was based, to the Sponsor, 
prior to commencing the clinical investigation.  
iii. 
Submit the following to the IEC if required by national regulations, the protocol or 
IEC, whichever is more stringent: 
1. 
SAEs 
2. 
Requests for deviations, and reports of deviations, if the deviation affects 
subject’s rights, safety, and well-being, or the scientific integrity of the clinical 
investigation. Document and report to the Sponsor and IEC a report of 
deviations made to protect the rights, safety, and well-being of human 
subjects under emergency circumstances.  
3. 
Progress reports, including safety summary and deviations 
4. 
Amendments to any documents already approved by the IEC.  

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 88 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
5. 
If applicable, notifications of suspension or premature termination 
6. 
If applicable, justification and request for resuming the clinical investigation 
after suspension.  
7. 
Clinical investigation report or summary. 
iv. 
As a minimum, during the clinical investigation, the following information shall be 
obtained in writing from the IEC prior to implementation: 
1. 
Approval/favorable opinion of amendments 
2. 
Approval of the request for deviations that can affect the subject’s rights, 
safety, and well-being or scientific integrity of the clinical investigation 
3. 
Approval for resumption of a suspended clinical investigation if applicable.  
c. 
obtain the written and dated approval/favorable opinion of the IEC for the clinical 
investigation before recruiting subjects and implementing all subsequent amendments, 
if required, 
d. 
promptly report any deviations from the protocol 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 IEC, protocol or 
national regulations. In particular circumstances, the communication with the IEC 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 PI shall: 
a. 
General: 
i. 
Informed consent shall be obtained in writing from the subject and the process 
shall be documented before any procedure specific to the clinical investigation is 
applied to the subject; except when special circumstances for emergency 
treatments apply (see below) 
b. 
Process of obtaining informed consent. The general process for obtaining informed 
consent shall be documented in the protocol and shall comply with the following. These 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 89 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
requirements also apply with respect to informed consent obtained from a subject’s 
legally authorized representative:  
i. 
Ensure that the PI or his/her authorized designee conducts the informed consent 
process 
ii. 
Include all aspects of the clinical investigation that are relevant to the subject’s 
decision to participate throughout the clinical investigation 
iii. 
Avoid any coercion or undue improper influence on, or inducement of, the subject 
to participate 
iv. 
Not waive or appear to waive the subject’s legal rights 
v. 
Use native non-technical language that is understandable to the subject 
vi. 
Provide ample time for the subject to read and understand the informed consent 
form and to consider participation in the clinical investigation 
vii. 
Include personally dated signatures and the PI or an authorized designee 
responsible for conducting the informed consent process 
viii. 
Show how informed consent will be obtained in special circumstances (see below) 
where the subject is unable to provide him or herself, and  
ix. 
Ensure important new information is provided to new and existing subjects 
throughout the clinical investigation.  
c. 
Special circumstances for informed consent (the following provisions are subject to 
national regulations): 
i. 
Subject needing legally authorized representatives:  informed consent may be 
given by the legally authorized representative only if a subject is unable to make 
the decision to participate in a clinical investigation (e.g., infant, child, or juvenile, 
seriously ill or unconscious subject, mentally ill person, mentally handicapped 
person). In such cases, the subject shall also be informed about the clinical 
investigation within his/her ability to understand.  
ii. 
Subject unable to read or write: informed consent shall be obtained through a 
supervised oral process if a subject or legally authorized representative is unable 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 90 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
to read or write. An independent witness shall be present throughout the process. 
The written informed consent form and any other information shall be read aloud 
and explained to the prospective subject or his/her legally authorized 
representative and, whenever possible, either shall sign and personally date the 
informed consent form. The witness also signs and personally dates the informed 
consent for attesting that the information was accurately explained and that the 
informed consent was freely given.  
iii. 
Emergency treatments:  
1. 
For clinical investigations involving emergency treatments, when prior 
informed consent of the subject is not possible because of the subject’s 
medical condition, the informed consent of the subject’s legally authorized 
representative, if present, shall be requested.  
2. 
When it is not possible to obtain prior informed consent from the subject, and 
the subject’s legally authorized representative, is not available, the subject 
may still be enrolled if a specific process has been described in the protocol.  
3. 
Arrangements shall be made to inform the subject or legally authorized 
representative, as soon as possible, about the subject’s inclusion in the 
clinical investigation and about all aspects of the clinical investigation.  
4. 
The subject shall be asked to provide informed consent for continued 
participation as soon as his/her medical condition allows.  
d. 
The Principal Investigator may not enroll a subject without obtaining informed consent 
of the subject or his/her legally authorized representative only when the following 
conditions are fulfilled: the prospective subject fulfils the emergency conditions and is 
obviously in a life-threatening situation; no sufficient clinical benefits are anticipated 
from the currently available treatment; there is a fair possibility that the life-threatening 
risk to the prospective subject can be avoided if the investigational device is used; 
anticipated risks are outweighed by the potential benefits of applying the investigational 
device ; the legally authorized representative cannot be promptly reached and informed.  

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 91 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
e. 
Information provided to the subject. All information pertinent to the clinical investigation, 
including at least the following, shall be provided in writing and in native, non-technical 
language that is understandable to the subject (or the subject’s legally authorized 
representative): 
i. 
Description and purpose 
ii. 
Potential benefits 
iii. 
Risks and inconveniences or the subject and, when applicable, for any embryo, 
fetus or nursing infant 
iv. 
Alternative procedures 
v. 
Confidentiality 
vi. 
Compensation 
vii. 
Anticipated expenses, if any, to be borne by the subject for participating in the 
clinical investigation 
viii. 
Information on the role of Sponsor’s representative in the clinical investigation 
ix. 
Contact persons 
x. 
Statement declaring that new findings or the reasons for any amendment to the 
protocol that affect the subject’s continued participation shall be made available to 
the subject.  
xi. 
Statement indicating that, upon the subject’s approval, the subject’s personal 
physician will be informed of the subject’s participation in the clinical investigation 
xii. 
Termination procedures 
f. 
Informed consent signature shall contain the following:  
i. 
The voluntary agreement to participate in the clinical investigation and follow the 
investigator’s instructions 
ii. 
A statement declaring that refusal of participation incurs no penalty for the subject 
iii. 
A statement declaring that discontinuation at any time incurs no penalty for the 
subject 
iv. 
A statement with regard to the possible consequences of withdrawal 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 92 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
v. 
An acknowledgment of the information provided and confirmation that all the 
subject’s questions were answered 
vi. 
A statement confirming that the subject or his/her legally authorized 
representative agrees to the use of the subject’s relevant personal data for the 
purpose of the clinical investigation 
vii. 
A statement confirming that the subject or his/her legally authorized 
representative agrees that Sponsor’s representatives, regulatory authorities and 
IEC representatives will be granted direct access to the subject’s medical records.  
g. 
New information: if new information becomes available that can significantly affect a 
subject’s future health and medical care, that information shall be provided to the 
subject(s) affected in written form. If relevant, all affected subjects shall be asked to 
confirm their continuing consent in writing.  
h. 
Ensure compliance with the applicable regulatory requirements and ethical principles 
for the process of obtaining informed consent, and 
i. 
Ensure and document appropriate training if an authorized designee is appointed to 
conduct the informed consent process. 
6. Compliance with the protocol. The Principal Investigator shall: 
a. 
indicate his/her acceptance of the protocol in writing, 
b. 
conduct the clinical investigation in compliance with the protocol, 
c. 
create and maintain source documents throughout the clinical investigation and make 
them available as requested during monitoring visits or audits, 
d. 
ensure that the investigational device is used solely by authorized users as specified in 
6.2, and in accordance with the protocol and instructions for use, 
e. 
propose to the Sponsor any appropriate modification(s) of the protocol or investigational 
device or of the use of the investigational device, 
f. 
refrain from implementing any modifications to the protocol without agreement from the 
Sponsor, IEC and regulatory authorities, if required, 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 93 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
g. 
document and explain any deviation from the approved protocol 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, 
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 CRF and in all required reports, 
k. 
maintain the device accountability records, 
l. 
allow and support the Sponsor to perform monitoring and auditing activities, 
m. be accessible to the monitor and respond to questions during monitoring visits, 
n. 
allow and support regulatory authorities and the IEC when performing auditing 
activities, 
o. 
ensure that all clinical-investigation-related records are retained as required taking 
measures to prevent accidental or premature destruction, and 
p. 
review and sign the clinical investigation report, as applicable. 
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,  
b. 
inform the subject of the nature and possible cause of any adverse events experienced, 
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 may 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 

 
Study Protocol 
A prospective, multi-center, single arm PMCF study to evaluate 
the safety and performance of ENTACT™ (Next Generation) 
resorbable septal staple system for septoplasty 
Number: 
ENTACT.ENT.PRO.SEP.2019.05 
Version: 2.0, 27Aug2020 
Page: Page 94 of 94 
 
 
 
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.  
 
TMP-CD-05-01 – Clinical Protocol-Device – Revision A; SOP-CD-05 Clinical Protocols 
 
 
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, subjects enrolled in the clinical investigation shall be provided with some 
means of showing their participation in the clinical investigation, 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 or when required by national regulations, the 
subject's personal physician about the subject's participation in the clinical investigation, 
and  
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, 
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 protocol, 
c. 
report to the IEC serious adverse events and device deficiencies that could have led to 
a serious adverse device effect, if required by the national regulations or protocol or by 
the IEC, 
d. 
report to regulatory authorities serious adverse events and device deficiencies that 
could have led to a serious adverse device effect, as required by the national 
regulations, and 
e. 
supply the Sponsor, upon Sponsor's request, with any additional information related to 
the safety reporting of a particular event. 

Certificate Of Completion
Envelope Id: 930EB5F1D9B4464AA0CAEE5AC314BAB9
Status: Completed
Subject: Please DocuSign: 2020 08.27 ENTACT Study Protocol Version 2.0  Clean Version pdf.pdf
Source Envelope: 
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Esvanhnelly Podany
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