A Retrospective Multicenter Study to Review the Use of Simplex High Viscosity Bone Cement in Primary Total Knee Arthroplasty
Conditions: Arthritis Knee, Aseptic Loosening
Sponsor: Stryker Orthopaedics

 
CONFIDENTIAL 
This material is the property of Stryker Orthopaedics.  Do not disclose or use except as authorized in writing by Stryker. 
  
 
 
 
 
 
Simplex HV Bone Cement 
 
CLINICAL PROTOCOL 
 
A Retrospective Multicenter Study to Review the Use of Simplex High Viscosity Bone 
Cement in Primary Total Knee Arthroplasty 
 
Sponsor: 
Stryker Orthopaedics 
325 Corporate Drive 
Mahwah, NJ 07430 
201-831-5000 
EU legal representative: 
Stryker European Operations Ltd 
IDA Business Park Anngrove 
Carrigtwohill, Co. Cork 
Ireland 
Study Product: 
Bone Cement: 
Simplex® HV  
Simplex® HV with Gentamicin  
Protocol Number: 
80 
510(k) Clearance Number: 
K123225 Simplex HV 
K123081 Simplex HV with Gentamicin 
Written by  
Britta von den Brincken 
Clinical Study Manager 
Stryker GmbH & Co.KG 
Dr.-Homer-Stryker-Platz 1 
47228 Duisburg, Germany 
0049 1638999202 
Date:  
Version  
20 January 2020 
1.0 
 
CONFIDENTIAL 
 
This document is confidential and the property of Stryker Orthopaedics. No part of it may be 
transmitted, reproduced, published or used by other persons without prior written authorization 
from Stryker Orthopaedics. 
 
 

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Protocol Change History 
 
 
Version 
Description 
Justification for 
change 
Changed By 
A 
New 
 
 
1.0 
Final 
NA 
 

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Table of Contents 
STUDY SYNOPSIS ....................................................................................................................................... 6 
EVALUATION SCHEDULE .......................................................................................................................... 8 
1 
INTRODUCTION .................................................................................................................................. 8 
1.1 
BACKGROUND ................................................................................................................................ 8 
1.2 
CLINICAL DATA TO DATE................................................................................................................. 9 
2 
CLINICAL STUDY PLAN ..................................................................................................................... 9 
2.1 
STUDY DESIGN .............................................................................................................................. 9 
2.2 
STUDY CENTERS ............................................................................................................................ 9 
2.3 
NUMBER OF SUBJECTS ................................................................................................................... 9 
3 
DEVICE DESCRIPTION .................................................................................................................... 10 
3.1 
STUDY DEVICE ............................................................................................................................. 10 
3.1.1 
Simplex HV Non-medicated Orthopaedic Cement ................................................................ 10 
3.1.2 
Simplex HV with Gentamicin ................................................................................................. 11 
3.2 
ANCILLARY DEVICES .................................................................................................................... 12 
4 
STUDY PROCEDURES ..................................................................................................................... 12 
4.1 
SUBJECT RECRUITMENT AND SCREENING ..................................................................................... 12 
4.2 
PATIENT INFORMED CONSENT AND GUIDELINES............................................................................. 12 
5 
STUDY DETAILS ............................................................................................................................... 12 
5.1 
INCLUSION/EXCLUSION CRITERIA .................................................................................................. 12 
5.2 
PRE-OPERATIVE DATA COLLECTION .............................................................................................. 13 
5.3 
INTRA-OPERATIVE DATA COLLECTION ........................................................................................... 13 
5.4 
POST-OPERATIVE DATA COLLECTION ............................................................................................ 14 
6 
ADVERSE EVENTS ........................................................................................................................... 14 
6.1 
REPORTING OF ADVERSE EVENTS ................................................................................................ 14 
6.2 
GENERAL ADVERSE EVENT DEFINITIONS ....................................................................................... 15 
6.3 
STUDY SPONSOR NOTIFICATION BY INVESTIGATOR ........................................................................ 17 
6.3.1 
Ethics Committee/Institutional Review Board Notification by Investigator ............................ 18 
6.4 
MEDICAL MONITORING ................................................................................................................. 18 
7 
X-RAY ANALYSIS ............................................................................................................................. 19 
7.1 
DEFINITON OF ASEPTIC LOOSENING .............................................................................................. 19 
8 
DATA MANAGEMENT ...................................................................................................................... 19 
8.1 
DATABASE ................................................................................................................................... 19 
8.2 
CONFIDENTIALITY ......................................................................................................................... 19 
8.3 
SOURCE DOCUMENTS .................................................................................................................. 20 
8.4 
DATA CLARIFICATION REQUESTS .................................................................................................. 20 
8.5 
PROTOCOL DEVIATIONS ............................................................................................................... 20 
8.6 
RECORDS RETENTION .................................................................................................................. 20 
9 
STATISTICAL PLAN ......................................................................................................................... 21 
9.1 
STUDY OBJECTIVES ..................................................................................................................... 21 
9.1.1 
Objective Analysis ................................................................................................................. 21 
9.2 
SAFETY ....................................................................................................................................... 21 
9.2.1 
Safety Parameters ................................................................................................................. 21 
9.2.2 
Safety Analyses ..................................................................................................................... 21 
9.3 
MISSING DATA ............................................................................................................................. 21 
9.4 
STATISTICAL METHODOLOGY ........................................................................................................ 21 
9.4.1 
Data Summary....................................................................................................................... 21 

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9.4.2 
Sample Size Justification ...................................................................................................... 22 
9.4.3 
Interim Analyses .................................................................................................................... 22 
9.4.4 
Analysis Population ............................................................................................................... 22 
10 
STUDY MONITORING, AUDITING, AND INSPECTING .................................................................. 22 
10.1 
STUDY MONITORING PLAN ............................................................................................................ 22 
10.2 
AUDITING AND INSPECTING ........................................................................................................... 23 
11 
PUBLICATION PLAN ........................................................................................................................ 23 
12 
RISK/BENEFIT ASSESSMENT ......................................................................................................... 24 
12.1 
RISK CATEGORY, POTENTIAL RISK ................................................................................................ 24 
12.2 
EXPECTED COMPLICATIONS AND RATES OF OCCURRENCES ........................................................... 24 
12.3 
POTENTIAL BENEFITS TO THE SUBJECT ......................................................................................... 25 
13 
ETHICAL CONSIDERATIONS .......................................................................................................... 25 
14 
STUDY FINANCES ............................................................................................................................ 26 
14.1 
FUNDING SOURCE ........................................................................................................................ 26 
14.2 
CONFLICT OF INTEREST ................................................................................................................ 26 
14.3 
SUBJECT STIPENDS OR PAYMENTS ............................................................................................... 26 
15 
REFERENCES ................................................................................................................................... 26 
 
 
List of Tables 
Table 1 Evaluation Schedule ......................................................................................................................................... 8 
Table 2 Simplex HV non-medicated component composition ...................................................................................... 10 
Table 3 Simplex HV Gentamicin component composition ............................................................................................ 11 
Table 4 Initial AE report information ............................................................................................................................. 17 
Table 5 Possible roles of chair and PI .......................................................................................................................... 24 
 
List of Figures 
Figure 1 Adverse event decision tree ........................................................................................................................... 15 
Figure 2 Component zones .......................................................................................................................................... 19 
 
List of Appendices 
Appendix A Component Listing .................................................................................................................................... 28 
Appendix B Case Report Forms................................................................................................................................... 30 
Appendix C 510k Clearance Letters............................................................................................................................. 44 
Appendix D Instructions for Use ................................................................................................................................... 56 
 
 
 
 
 
 
 

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CONFIDENTIAL 
This material is the property of Stryker Orthopaedics.  Do not disclose or use except as authorized in writing by Stryker. 
List of Abbreviations 
 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BMI 
Body Mass Index 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CSM 
Clinical Study Manager 
DCR 
Data Clarification Request 
EC 
Ethics Committee 
HV 
High Viscosity 
IRB 
Institutional Review Board 
KSS 
Knee Society Score 
OKS 
Oxford Knee Score 
PROMs 
Patient Reported Outcome Measures 
QoL 
Quality of Life 
ROM 
Range of Motion 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SC 
Study Coordinator 
TKA 
Total Knee Arthroplasty 
UADE 
Unanticipated Adverse Device Effect 
 
 

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Study Synopsis 
Title 
A Retrospective Multicenter Study to Review the Use of Simplex 
High Viscosity Bone Cement in Primary Total Knee Arthroplasty  
Short Title 
Simplex HV 
Protocol Number 
80 
Phase 
Post Market 
Methodology 
International, multicenter, retrospective follow-up of a consecutive 
series of patients  
Study Duration 
Examination of retrospective patient data from a determined 
period of 24 months, optional 5 years including pre-operative and 
intra-operative assessment 
Number of Centers 
2-5 
Objectives 
Primary: 
To evaluate the success rate of cemented Triathlon Total Knee 
components implanted using Simplex high viscosity bone cement 
(Simplex HV). Success is defined as absence of revision due to 
aseptic loosening in cemented Triathlon Total Knee components 
implanted with Simplex HV at 24 months. 
Secondary: 
To review OKS, KSS results and complications of patients who 
have received Simplex HV in a Triathlon Total Knee Arthroplasty. 
Number of Cases 
A minimum of 100 Simplex HV cases and 100 Simplex HV-
Gentamicin cases who have received cemented Triathlon Total 
Knee System will be enrolled. 
Inclusion/Exclusion 
Criteria 
Inclusion Criteria: 
A. The Patient is age 18 or over at time of study device 
implantation 
B. Patients who have undergone primary Triathlon Total 
Knee Arthroplasty in which Simplex HV/Simplex HV 
Gentamicin was indicated for fixation and used on label 
C. Patients who have been followed for at least 24 months 
postoperatively 
 
Exclusion Criteria: 
A. Patients who have undergone revision surgery 
B. Patients who have undergone bilateral Knee Arthroplasty 
C. Patients contraindicated for either the devices implanted, 
or the cement used, according to medical history review 
and instructions for use  
D. Patient has a cementless tibial baseplate. 
E. Patient has an active or suspected latent infection in or 
about the affected knee joint 
F. Patient has muscle loss or neuromuscular impairment in 
the affected limb that would create an unjustifiable risk  

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G. Patient is immunologically suppressed or receiving 
steroids in excess of normal physiological requirements 
(e.g. > 30 days) 
H. Patient has a known hypersensitivity to any of the cements 
constituents or in patients with severe renal failure 
I. Patient is a prisoner 
Study Device 
Bone Cement: 
• 
Simplex® HV  
• 
Simplex® HV with Gentamicin  
Statistical Methodology 
• 
No sample size calculation because a number of 100 cases 
per study arm was pre-defined by the regulatory body.  
• 
The success rate at two years will be presented with 95% 
confidence interval.   
• 
Frequency and percentage will be presented in tabular form 
for categorical variables. The mean, standard deviation, 
minimum and maximum values will be presented for 
quantitative variables. 
 
 
 

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Evaluation Schedule 
Evaluation 
Pre- 
operative  
Intra-
operative 
24 (+2) 
months 
post-
operative  
27 months 
up to 5 
years post- 
operative 
Inclusion/Exclusion 
x 
 
 
 
Demographics & Medical History 
x 
 
 
 
KSS 
x 
 
x 
optional 
Surgical Details 
 
x 
 
 
Implant and Cement Details 
 
x 
 
 
OKS 
x 
 
x 
optional 
A/P and Lateral X-ray Interface 
 
 
x 
optional 
Adverse Events 
 
x 
x 
per protocol 
Table 1 Evaluation Schedule 
 
 
 
This document is a protocol for a retrospective human research study. This study will be 
conducted in compliance with the protocol, international standard ISO 14155 Standards, 
associated Federal regulations and all applicable research requirements.  
1.1 Background 
The American Joint Replacement Registry (AJRR) shows an annual increase from approximately 
20,000 to almost 130,000 in primary TKAs from 2012 to 2017. In the same time the use of High 
Viscosity Cement (HVC) in primary knee arthroplasty increased steadily from 46% to 61%1. 
Most of commercially available acrylic bone cements are based upon polymethylmethacrylate 
(PMMA) and methylmethacrylate (MMA) systems and consist of powdered and liquid 
components2. The polymerization of bone cement occurs through a progression of 4 phases: 
mixing phase, waiting phase, working phase, and hardening phase. HVC has some advantages 
over low-viscosity cement (LVC) including shorter mixing and waiting phases, whereas the 
working and hardening phases are longer. Operational efficiencies are receiving greater interest 
by surgeons and hospital administrations because high viscosity (HV) bone cements provide a 
shorter dough time than medium viscosity cements, which may result in surgical efficiencies by 
1 Introduction 

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allowing surgeons to handle and apply the cement to implant components and bone earlier while 
having more time to work with the cement during implantation of the components.1,2,3.  
The most common reason for failure of TKA is infection followed by implant loosening, 
polyethylene wear, and instability4. With the use of HVC, the literature describes a focus on 
aseptic loosening of the tibial component probably resulting from debonding of the cement-tray 
interface3,4. Considering the exact cause may be unknown, some authors suggest associations 
of this type of failure to the use of high-viscosity cement 5,6. In contrast, a retrospective review of 
1851 cases of primary TKA (obese patients with BMI >35) using HVC mixed with Gentamicin 
showed one revision due to aseptic loosening3. 
This study is a retrospective investigation of subjects who have received primary Triathlon Total 
Knee Arthroplasty inserted with Simplex High Viscosity (HV) Cement to evaluate the success rate 
defined as absence of revision for aseptic loosening of components at two years postoperative. 
1.2 Clinical Data to Date 
This study is the first Stryker Joint Replacement sponsored retrospective data collection on the 
Simplex HV bone cement. 
 
2 Clinical Study Plan 
2.1 Study Design 
A retrospective, post-market, multi-center design will be employed.  
2.2 Study Centers 
Cases will be enrolled retrospectively at two to five centers which will enroll a minimum of 100 
cases with Simplex HV non-medicated and 100 cases with Simplex HV with Gentamicin. All 
participating centers will comply with the federal regulations and apply at the responsible 
Institutional Review Board (IRB) or Ethics Committee (EC) for patient informed consent waiver. 
Non-compliance of a study center may result in termination of the center’s participation in the 
study. 
2.3 Number of Subjects 
Cases will be enrolled until a total of 100 cases with Simplex HV non-medicated and 100 cases 
with Simplex HV with Gentamicin were observed and collected. Depending on the hospital 

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standard of care, a site may only enroll subjects receiving Simplex HV non-medicated and another 
site may only enroll subjects receiving Simplex HV with Gentamicin. 
3 Device Description 
3.1 Study Device 
Simplex HV is available non-medicated and medicated with Gentamicin antibiotic. 
The US listing number are Simplex HV: D295829 and Simplex HV with Gentamicin: D295830. 
The Simplex HV bone cement is FDA recognized and registered under D-U-N-S-Number 
3442616311. 
Simplex HV with Gentamicin is registered in the Australian Register of Therapeutic Goods (ARTG) 
under 276417. 
Simplex HV/Gentamicin is CE certified under 135-0581-01 and Simplex HV under 135-0595-01. 
3.1.1 Simplex HV Non-medicated Orthopaedic Cement 
Simplex HV bone cement is a fast-setting acrylic resin for use in bone surgery. Mixing the two 
separate sterile components produces a ductile bone cement which, after hardening, fixes the 
implant and transfers stresses produced during movement evenly to the bone. Simplex HV 
cement powder also contains insoluble zirconium dioxide as an X-ray contrast medium. Simplex 
HV does not emit a signal and does not pose a safety risk in a magnetic resonance environment. 
Simplex HV is a substance designed to be used in arthroplastic and/or osteosynthetic procedures 
for the fixation of polymer or metallic implants to the living bone. It is typically made from 
methylmethacrylate, polymethylmethacrylate (PMMA)2, esters of methacrylic acid or copolymers 
containing polymethylmethacrylate and polystyrene. This device does not contain an antimicrobial 
agent. The option for high viscosity does not compromise depth of intrusion. After application, this 
device cannot be reused.  
Table 2 Simplex HV non-medicated component composition 
 
1The FDA formally recognized the D-U-N-S-Number as an acceptable unique facility identifier (UFI) for the Foreign Supplier 
Verification Programs (FSVP). The identification of importers will help the FDA effectively implement, monitor compliance with, and 
enforce the FSVP requirements. 
2 Simplex HV bone cement contains 40g polymethyl methacrylate (PMMA) powder and 20 ml methylmethacrylate 
  (MMA) liquid.  
 
Composition of cement powder: 
40g Composition of liquid: 
20ml 
Poly 
(methylacrylate/methylmethacrylate) 
33.7 g Methylmethacrylate (stabilized 
with 60 ppm HQ) 
18.4 g 
Zirconium dioxide 
6 g N,N-dimethyl-p-toluidine 
0.4 g 
Benzoyl peroxide 
0.3 g  
 

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In partial or total replacement of the hip, knee and other joints, Simplex HV is indicated for fixation 
of synthetic resin polymer and metal prosthesis components in uninfected vital bones if joint 
reconstruction is required. In tumour surgery, Simplex HV is used in combination with internal 
fixation to fill bone cavities after tumour removal. 
The use of Simplex HV is contraindicated if muscle wasting or neuromuscular compromise in the 
affected limb renders the procedure unjustifiable. Simplex HV should not be used in the event of 
known hypersensitivity to any of its constituents or if there are active or inadequately treated 
infections in the region of the implant. 
3.1.2 Simplex HV with Gentamicin 
Simplex HV bone cement with Gentamicin is a fast-setting acrylic resin with addition of 
Gentamicin sulfate for use in bone surgery. The added antibiotic, Gentamicin sulfate, protects the 
implant and the surrounding tissue from colonization with pathogens that are sensitive to 
gentamicin. Simplex HV with Gentamicin cement powder also contains insoluble zirconiumdioxide 
as an X-ray contrast medium. Simplex HV with Gentamicin does not emit a signal and does not 
pose a safety risk in a magnetic resonance environment. 
Mixing the two separate sterile components produces a ductile bone cement which after 
hardening, fixes the implant and transfers stresses produced during movement evenly to the 
bone. 
Composition of cement powder: 
40.8 g Composition of liquid: 
20ml 
Poly 
(methylacrylate/methylmethacrylate) 
33.7 g Methylmethacrylate (stabilized 
with 60 ppm HQ) 
18.4 g 
Zirconium dioxide 
6 g N,N-dimethyl-p-toluidine 
0.4 g 
Benzoyl peroxide 
0.3 g  
 
Gentamicin base 
(added as Gentamicin sulfate) 
0.5 g 
(0.8 g)  
 
Table 3 Simplex HV Gentamicin component composition 
 
Simplex HV with Gentamicin is indicated for fixation of synthetic resin and metal prosthesis 
components during partial or total replacement of the hip and knee as well as other joints, if an 
infection with organisms that are sensitive to gentamicin is diagnosed or suspected. The antibiotic 
provides protection against bacterial colonization of the implant and the surrounding tissue. 
Simplex HV with Gentamicin can be used for filling and stabilizing bone defects within the scope 
of internal fixation treatment, if there is an increased risk of infection with pathogens that are 
sensitive to gentamicin. 
The use of Simplex HV with Gentamicin is contraindicated, if muscle wasting or neuromuscular 

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compromise in the affected limb renders the procedure unjustifiable. Simplex HV with Gentamicin 
should not be used in the event of known hypersensitivity to any of its constituents or in patients 
with severe renal failure. 
3.2 Ancillary Devices 
Additionally, only the following Stryker Orthopaedics compatible ancillary devices may be used, 
according to this study protocol: 
o Triathlon Total Knee System 
 
4 Study Procedures 
4.1 Subject Recruitment and Screening 
 
Subjects will be enrolled at the study centers using the electronic medical record, paper charts, 
information from pre- and postoperative images, intraoperative notes, and follow-up data collected 
as part of the hospital’s routine care. The eligibility of these subjects will be assessed, according 
to the inclusion/ exclusion criteria.  
All personal identifiable patient information will be pseudonymized and tracked via a unique 
subject number, known only to the site. Data extracted from the subject hospital files (paper or 
electronically stored); will be entered into paper case report forms (CRF).  
4.2 Patient Informed Consent and Guidelines 
 
The study protocol will be submitted for IRB/ EC Review. As pseudonymized retrospective patient 
data will be used, a requirement for informed consent is not expected, however waiver of consent 
from the IRB/EC is required. 
5 Study Details 
5.1 Inclusion/Exclusion Criteria 
Inclusion Criteria: 
A. The Patient is age 18 or over at time of study device implantation 
B. Patients who have undergone primary Triathlon Total Knee Arthroplasty in which 
Simplex HV/Simplex HV Gentamicin was indicated for fixation and used on label 
C. Patients who have been followed for at least 24 months postoperatively 
 
 

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Exclusion Criteria: 
A. Patients who have undergone revision surgery 
B. Patients who have undergone bilateral Knee Arthroplasty 
C. Patients contraindicated for either the devices implanted, or the cement used, according 
to medical history review and instructions for use  
D. Patient has a cementless tibial baseplate. 
E. Patient has an active or suspected latent infection in or about the affected knee joint 
F. Patient has muscle loss or neuromuscular impairment in the affected limb that would 
create an unjustifiable risk  
G. Patient is immunologically suppressed or receiving steroids in excess of normal 
physiological requirements (e.g. > 30 days) 
H. Patient has a known hypersensitivity to any of the cements constituents or in patients 
with severe renal failure 
I. Patient is a prisoner 
5.2 Pre-operative Data Collection 
• 
Patient demographics  
• 
Diagnosis/reason for the primary total knee arthroplasty, operative side 
• 
Preoperative medical history: Relevant concurrent medical condition and treatment 
• 
Knee Society Score (KSS)  
• 
Oxford Knee Score 
5.3 Intra-operative Data Collection 
• 
Surgical details 
o Type of anesthesia 
o Anesthesia class ASA 
o Systemic prophylactic therapy 
o Surgical approach 
o Surgeon initials 
o Skin to skin and tourniquet time 
o Blood loss  
• 
Simplex HV details 
o Cement storing temperature 
o Operating room temperature 
o Cement type 

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o Cement use 
o Cement preparation 
• 
Triathlon Total Knee Replacement details 
o Femoral component 
o Tibial component 
• 
Intra-operative Adverse event or device deficiency  
5.4 Post-operative Data Collection 
Data collection at 24 months (+ 2 months) postoperatively and optional at 5 years postoperative. 
• 
Knee Society Score (KSS)  
• 
Oxford Knee Score (OKS) 
• 
X-ray collection for independent analysis  
o A/P view 
o Lateral view 
• 
Elective surgery since study surgery 
• 
Post-operative Adverse event or device deficiency 
6 Adverse Events 
6.1 Reporting of Adverse Events 
The AE reporting requirements for this study are as follows: 
• 
All AEs that meet the definition of serious  
• 
All AEs related to the operative site, regardless of seriousness or time of occurrence 
On retrospective review of postoperative data, investigators and study coordinators (SCs) will 
search the subject’s hospital files as to whether they have seen a doctor for any reason, been 
hospitalized for any reason or have a current impediment to their function. 
If it is determined upon this further investigation that a protocol-defined AE has occurred, the SC 
will be responsible to complete an AE CRF. If the event is related or uncertain related to the 
Triathlon TKA or to Simplex HV, the investigator will verify if the event has been reported to Stryker 
at time point of occurrence or will report at time point of data review at the latest. The event shall 
be reported to Stryker and to the IRB/EC, as required. 
 
The following decision tree facilitates identification of AEs for which reporting is required under 
this study protocol: 
 
 

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Figure 1. Adverse Event Decision Tree 
Do NOT report to Stryker
Is the AE
related to the operative
side?
AE finding in the
retrospective data review
Complete AE form
Does the AE 
meet the criteria for 
seriousness?
End
no
no
yes
yes
 
Figure 1 Adverse event decision tree 
 
General Retrospective Review Findings 
At screening for inclusion into the study, any clinically significant abnormality should be recorded 
as a preexisting condition and reported on the Demographics CRF. From the time of surgery 
forward, any new clinically significant findings or abnormalities that meet the definition of a 
protocol defined AE must also be recorded and documented as an AE until the end of the 
observation period or maximum at the five years follow-up. 
Adverse Event Reporting Period 
The study period during which AEs must be reported is defined as the period from the surgery to 
the last protocol specified follow-up.  
During retrospective review of the subject’s hospital files, information on protocol defined AEs 
shall be recorded in the AE CRF. The clinical course of each event should be followed until 
resolution or until it is determined at the end of the study that the AE will not resolve. 
6.2 General Adverse Event Definitions 
Following is a list of general AE definitions. For the purposes of this study, only SAEs, excluding 
elective procedures, as well as all AEs related to the operative site should be reported.  

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Adverse Event 
An AE is any untoward medical occurrence, in a clinical investigation subject which changes the 
medical baseline of the subject, users or other persons. An AE can be an unfavorable and 
unintended sign, symptom or disease, whether or not related to the study device (AEs may also 
be referred to as complications). See Section 6.1, Reporting of Adverse Events, for the AE 
reporting requirements for this study. 
NOTE 1 This definition includes events related to the investigational medical device or the comparator. 
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 investigational medical devices. 
Anticipated Adverse Event 
An anticipated AE is an AE, of which the nature, severity or degree of incidence is known and 
identified in applicable product labeling, published literature or the study protocol. The list of 
anticipated events is provided in Section 12, Risk/Benefit Assessment. 
Serious Adverse Event 
A SAE meets one or more of the following definitions: 
• 
led to death, 
• 
led to serious deterioration in the health of the subject, that either resulted in 
• 
a life-threatening illness or injury, or 
• 
a permanent impairment of a body structure or a body function, or 
• 
in-patient or prolonged hospitalization, or 
• 
medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
• 
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 protocol, without serious 
deterioration in health, is not considered a serious adverse event 
Adverse Device Effect 
An adverse device effect (ADE) is a negative change in the subject’s health that may have been 
caused by, or associated with, the use of the device. 
 
 

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Unanticipated Adverse Device Effect 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health, safety 
or any life-threatening problem or death caused by, or associated with, a device if that effect is a 
problem or death not previously identified in nature, severity or degree of incidence, or any other 
unanticipated serious problem associated with a device and related to the rights, safety or welfare 
of subjects. 
Device Deficiency 
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. Device deficiencies that did not lead to an adverse 
event but could have led to a medical occurrence 
a) if either suitable action had not been taken, 
b) if intervention had not been made, or 
c) if circumstances had been less fortunate 
NOTE Device deficiencies include malfunctions, use errors, and inadequate labelling. 
6.3 Study Sponsor Notification by Investigator 
Of reportable AEs, certain events must be submitted to Stryker Orthopaedics within 24 hours for 
timely notification: 
Adverse events that require time sensitive reporting: 
An adverse event should be reported to Stryker Orthopaedics Clinical Research either by 
telephone/fax/email within 24 hours after retrospective finding of the event if any of the following 
apply: 
• 
The AE occurs intraoperatively or is related to the surgical procedure. 
• 
The AE is considered by the investigator to be Simplex HV related or if the 
investigator is uncertain regarding the device related assessment; 
• 
The Simplex HV relation requires a reoperation of the Triathlon total knee 
arthroplasty 
At the time of the initial report, the following information should be provided: 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Current status 
• 
Whether study treatment was 
discontinued 
• 
Investigator assessment of the 
association between the event and 
the study treatment 
Table 4 Initial AE report information 
 

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These reports will be evaluated by Stryker Orthopaedics to determine if a Product Inquiry (PI) is 
required. 
6.3.1 Ethics Committee/Institutional Review Board Notification by Investigator 
Reports of AEs (including follow-up information) must be submitted to the EC or IRB 
according to their specific requirements. Copies of each report and documentation of 
EC/IRB notification and receipt will be kept with the investigator’s study files. 
6.4 Medical Monitoring 
It is the responsibility of the investigator to oversee the safety of the study at his/her center. This 
safety monitoring will include careful assessment and appropriate reporting of AEs, as previously 
noted. Stryker Orthopaedics will conduct formal investigations via the Product Surveillance 
Department of those AEs which are submitted through our PI System. 
 
 

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7 X-ray Analysis 
7.1 Definiton of Aseptic Loosening 
X-rays will be collected at least at two years after surgery for independent analysis of 
radiolucency occurence at implant-cement interface by an independent reviewer 
• 
Radiolucency at implant-cement interface 
o Tibia A/P 
o Tibia lateral 
o Femur PS lateral or Femur CR lateral 
Radiolucencies at the implant-cement interface more than 2 mm in all zones of a component is 
defined as aseptic loosening. 
 
Zones Tibia A/P7 
 
 
 
 
Zones Tibia  Lateral7 
 
 
Zones Femur PS Lateral7 
 
Zones Femur CR Lateral7 
 
 
Figure 2 Component zones 
 
8 Data Management 
8.1 Database 
Paper based data will be collected at each center and entered into Stryker Orthopaedics’s data 
base. 
8.2 Confidentiality 
This study will comply with the regional privacy rules. As such, Stryker Orthopaedics will only 
collect that information which is necessary to support the objectives of the clinical study. Stryker 

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Orthopaedics will take precautions to ensure that data received is de-identified as per regional 
privacy rules. In the case that some identified information is received, Stryker Orthopaedics will 
ensure that any identifying information is not publicly disclosed.  
8.3 Source Documents 
Source data include all information, original records of clinical findings, observations or other 
activities in a clinical study necessary for the reconstruction and evaluation of the study. Source 
data are contained in source documents. Examples of these original documents and data records 
include: hospital records, clinical and office charts, study worksheets, laboratory notes, 
memoranda, subject questionnaires, pharmacy dispensing records, recorded data from 
automated instruments, radiographs, subject files, and records kept at the pharmacy, at the 
laboratories and at medico-technical departments involved in the clinical study. 
Monitors, defined further in Section 10, will be comparing the documentation in CRFs against 
source documents for adequacy.  The monitors will seek to draw a reference between each data 
point on the CRF and the subject’s chart.  Every effort should be made to ensure complete source 
documentation.  
8.4 Data Clarification Requests 
If errors or omissions are noted by Stryker Orthopaedics upon review of the data entered into the 
CRFs, a data clarification request (DCR) will be sent to the center. Queries should be answered 
in a clear and comprehensible manner. If the clarification requires a change to study data, a copy 
of the DCR will be filed with the CRF.  
8.5 Protocol Deviations 
Any major deviation from this protocol will be recorded and must be reported to the EC/IRB by 
the investigational site according to their reporting procedures. Major protocol deviations for this 
study may include the following; this list may not be all-inclusive:  
• 
Patient enrolled does not meet the inclusion/exclusion criteria 
• 
Protocol specified study component(s) not implanted 
8.6 Records Retention 
It is the investigator’s responsibility to retain study essential documents for two years after the 
date of the final report, or in the case of non-compliance, two years after the date of investigative 
center termination.  These documents should be retained for a longer period if required by an 
agreement with Stryker. 

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9 Statistical Plan 
 
9.1 Study Objectives 
9.1.1 Objective Analysis 
To evaluate the success rate of cemented Triathlon Total Knee components implanted 
using Simplex high viscosity bone cement (Simplex HV). Success is defined as absence 
of revision of cemented Triathlon Total Knee components implanted with Simplex HV for 
aceptic lossening at two years postoperative. 95% confidence interval of the success rate 
will be presented as well.  
9.2 Safety 
9.2.1 Safety Parameters 
Safety parameters include all protocol-defined adverse events as well as revision and/or 
removal rates. For details regarding protocol-defined adverse events, see Section 6.1. 
9.2.2 Safety Analyses 
The frequency and percentage of all protocol-defined adverse events will be tabulated. 
For details regarding protocol-defined adverse events, see Section 6.1. 
9.3 Missing Data 
No missing data will be imputed 
9.4 Statistical Methodology 
9.4.1 Data Summary 
Descriptive statistics will be computed for all baseline conditions and demographic 
parameters. That is, for continuous data, the N, mean, median, standard deviation, 
minimum and maximum will be computed. For categorical data, the frequency will be 
computed. The data will be presented by appropriate subgroups (e.g., center, gender).  
A Kaplan-Meier survivorship curve will be displayed for revision and/or removal of the 
Triathlon total knee arthroplasty cemented with Simplex HV for aseptic loosening. 
A Kaplan-Meier survivorship curve will be displayed for all-cause revision and/or removal 
of the Triathlon total knee arthroplasty cemented with Simplex HV with Gentamicin for 
aseptic loosening.  

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Two year Kaplan-Meier success rate with 95% CI will be presented. 
For all additional data collected that are not required for direct support of a study objective, 
data will be summarized according to follow-up. For parameters represented by 
continuous variables (e.g., ROM), the summaries will consist of the N, mean, median, 
standard deviation, minimum, and maximum values.  
Documentation of statistical analyses utilizing SAS® software version 9.3 or higher will be 
maintained. 
9.4.2 Sample Size Justification 
No sample size calculation because a number of 100 cases per study arm was pre-
defined by the regulatory body.  
9.4.3 Interim Analyses 
No interim analysis is planned. Retrospective data up to five years will be analyzed. 
9.4.4 Analysis Population 
 
Per Protocol Population: The study population will include all non-censored subjects 
who have received the Triathlon total knee system cemented with Simplex HV and are 
available for objective analysis. 
The objective analyses will be based on the per protocol population.   
Safety Population: The safety population will include all non-censored subjects who 
received the Triathlon total knee system cemented with Simplex HV. 
The safety analysis will be based on the safety population. 
 
10 Study Monitoring, Auditing, and Inspecting 
10.1  Study Monitoring Plan 
Monitors/Clinical Research Associates (CRAs) are persons employed by sponsors to review the 
conduct of clinical studies to assure that the clinical investigators abide by their obligations to 
conduct clinical studies properly. Proper monitoring ensures adequate protection of the rights of 
human subjects, the safety of subjects involved in a clinical investigation and the quality and 
integrity of data submitted as a result of the investigation. 
This study will be monitored after documentation of retrospective data is done. The investigator 
will allocate adequate time for such monitoring activities. The investigator will also ensure that the 

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Monitor/CRA or other compliance or quality assurance reviewer is given access to all study-
related documents and study-related facilities, as applicable, and has adequate space to conduct 
the monitoring visit, when applicable. The Monitor/CRA will review all source documents and 
compare them to the data contained in the CRFs, in addition to performing a review of regulatory 
documents such as EC/IRB approvals. The Monitors/CRAs will need the following: 
• 
An area where they can review study data, when monitoring is conducted on site 
• 
Access to CRF data for all cases 
• 
Access to source documentation 
• 
Regulatory documents 
• 
Time to discuss findings with the SC and the investigator  
10.2  Auditing and Inspecting 
A quality assurance audit is a form of review that provides additional confidence to the sponsor 
concerning the validity and accuracy of clinical study data that must be submitted to the regulatory 
bodies or for publication. The purpose of investigator audits is to ensure that the investigator has 
maintained all study information according to the sponsor’s protocol and standard operating 
procedures and in compliance with regulations. 
 
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, 
Stryker Orthopaedics and/or government regulatory bodies of all study related documents (e.g. 
source documents, regulatory documents, data collection instruments, study data). The 
investigator will ensure the capability for inspections of applicable study-related facilities. 
 
11 Publication Plan 
 
It is anticipated that publication of the multi-center study results of an observation period over two 
years, with optional five year period, will be compiled and submitted to a peer-reviewed journal. 
Additional publication proposals may be made by investigators at any time and will be considered. 
This study will utilize the guidelines for authorship published by the International Committee of 
Medical Journal Editors (ICMJE). This guidance can be referenced at www.icmje.org. 
Publications will be facilitated by the Chair and the primary investigator (PI) of the study. Both 
individuals will be chosen by Stryker Orthopaedics. 
The PI is solely focused on the multi-center publications and progress towards those publications, 
including recurring updates to centers, center motivation as well as authorship. If the PI does not 

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produce a draft of a publication within 90 days of receiving the results data, Stryker Orthopaedics 
will delegate the responsibility to other investigators in the study at its discretion. 
The Chair reviews all additional publications proposed by participating investigators based upon 
the study results prior to study completion, on an ongoing basis.  This review includes whether or 
not a proposal will be pursued, as well as imposition of guidelines as to publication completion 
and criteria. 
The following summarizes the possible roles of these parallel positions: 
Chair 
PI 
Contributes to study design 
Contributes to study design 
Assists with study questions requiring expert 
clinical opinion 
Assists with study questions requiring expert 
clinical opinion 
Reviews additional publication proposals 
submitted by investigators 
Updates investigators on progress towards 
multi-center results 
Contributing author, if ICMJE guidelines met 
Primary author, multi-center publication of 
primary endpoint data 
Table 5 Possible roles of chair and PI 
 
At the completion of the study, each participating study investigator shall have independent 
publication privileges for his/her own center’s results. Although Stryker will not be involved in 
coordinating these independent manuscripts, all publications of the data shall be submitted to 
Stryker for review prior to submission for publication. Stryker shall not edit or otherwise influence 
the publications other than to ensure that confidential information is not disclosed, that no off-label 
use of Stryker devices is promoted and that the data is accurately represented.  Any publications 
resulting from this study must be submitted to Stryker for review at least 60 days prior to 
submission of publication. 
12 Risk/Benefit Assessment 
12.1  Risk Category, potential Risk 
There are no additional risks associated as the study is a retrospective review.  
12.2 Expected Complications and Rates of Occurrences 
In the retrospective data review it can be expected to find known complications. 
- Known complications after use of acrylate*: 
Intraoperative: 
Temporary drop in blood pressure immediately after application of cement, pulmonary 
embolism and mycardial infarctions in rare cases. 

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Post-operative: 
Temporary reduction in blood pressure, elevated blood serum levels diseases of the blood 
system, loosening of dislocation of the implant, wound infections, cardiovascular and 
pulmonary diseases, rare cases of anaphylaxis and sudden death. 
- Known complications after use of PMMA**: 
Allergic pyrexia, diseases of the urinary system, local neuropathy, vascular diseases, 
irritation of the siatic nerve. 
- Known complications causing from Simplex HV with Gentamicin: 
Hypertensitivity reactions, typical side effects of using Gentamicin which are extremely 
unlikely to occur because of the very low serum level of Gentamicin. 
For more details see “Adverse event” sections of IFU in Appendix D. 
* Liquid, see Tables 2 and 3 
** Powder, see Tables 2 and 3 
12.3  Potential Benefits to the Subject 
There is no guarantee that subjects will personally benefit from the retrospective data review 
within this study. This study seeks to provide clinicians information about Simplex HV bone 
cement. Information gathered in this study may benefit others undergoing TKA using Simplex HV 
bone cement in the future. 
 
13 Ethical Considerations 
 
This study is to be conducted for the protection of human subjects according to international 
standard ISO 14155 and applicable regional government regulations.  
 
This protocol and any amendments will be submitted to a properly constituted independent 
EC/IRB for formal approval of the study conduct. The decision of the EC/IRB concerning the 
conduct of the study will be made in writing to the investigator and a copy of this decision will be 
provided to Stryker Orthopaedics before commencement of this study. The investigator may be 
asked to provide a list of EC/IRB members and their affiliates to Stryker Orthopaedics, if available. 
An EC/IRB confirmation will be applied for waiver of patient information and informed consent due 
to collection of pseudonymized retrospective patient data. 
 
 

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14 Study Finances 
14.1 Funding Source 
This study is financed by Stryker. 
14.2 Conflict of Interest 
Any investigator who has a conflict of interest with this study (e.g. patent ownership, royalties or 
financial gain greater than the maximum allowable by their institution) must have the conflict 
reviewed by their EC/IRB or a properly constituted Conflict of Interest Committee with a 
Committee-sanctioned conflict management plan that has been reviewed and approved by 
Stryker prior to participation in this study.   
14.3 Subject Stipends or Payments 
Due to the Retrospective nature of this study, there will be no subject stipend or payment program.  
15 References 
 
 
 
1. Trends in the Use of High-Viscosity Cement in Patients Undergoing Primary Total Knee 
Arthroplasty in the United States 
Mick P. Kelly, MD, Richard L. Illgen, MD, Antonia F. Chen, MD, MBA, Denis Nam, MD, 
MSc 
The Journal of Arthroplasty 33 (2018) 3460e3464 
 
2. Comparative Handling, Intrusion and Antibiotic Elution Characteristics of Simplex HV 
Bone Cement 
Shulin He, Frank Sagato, Robert Klein, Hilda Mulvihill, Yehuda Bogatch 
Stryker CO, Mahwah, NJ, USA, Stryker CO, Limerick, Ireland 
 
3. Low Rates of Aseptic Tibial Loosening in Obese Patients With Use of High-Viscosity 
Cement and Standard Tibial Tray: 2-Year Minimum Follow-Up 
David A. Crawford, MD, Keith R. Berend, MD, Denis Nam, MD, Robert L. Barrack, MD, 
Joanne B. Adams, BFA, Adolph V. Lombardi Jr., MD, FACS 
The Journal of Arthroplasty 32 (2017) S183-S186 
 
4. Aseptic Tibial Debonding as a Cause of Early Failure in a Modern Total Knee 
Arthroplasty Design. 
Arsoy D, Pagnano MW, Lewallen DG, Hanssen AD, Sierra RJ.  
Clin Orthop Relat Res 2013; 471:94e101. 
 
5. Case Series Report: Early Cement–Implant Interface Fixation Failure in Total Knee 
Replacement 
Kyle J. Hazelwood, Michael O’Rourke, Van P. Stamos, Robert D. McMillan, David 
Beigler, William J. Robb III 
The Knee 22 (2015) 424–428 

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6. Failure at the Tibial Cement-Implant Interface with the Use of High Viscosity Cement in 
Total Knee Arthroplasty. 
Kopinski J, Aggarwal A, Nunley R, Barrack R, Nam D 
The Journal of Arthroplasty 2016; 31:2579  
 
7. Development of a Modern Knee Society Radiographic Evaluation System and 
Methodology for Total Knee Arthroplasty 
R.Michael Meneghini, Michael A.Mont, David B.Backstein, Doug A.Dennis,  
The Journal of Arthroplasty, Volume 30, Issue 12, 2015, 2311-2314 
 
 
 

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Appendix A Component Listing 
 
 
 
Study Device Component Listing: 
 
Catalogue Number 
Simplex HV Plain (non-medicated) 
6189-1-010 
Simplex HV Gentamicin 
6193-1-010 
 
 
 
Ancillary Component Listing: 
 
Triathlon 
Cemented Primary 
Tibial Baseplate 
 
 
 
 
 
 
5520-B-100 
 
 
 
 
 
 
5520-B-200 
 
 
 
 
 
 
5520-B-300 
 
 
 
 
 
 
5520-B-400 
 
 
 
 
 
 
5520-B-500 
 
 
 
 
 
 
5520-B-600 
 
 
 
 
 
 
5520-B-700 
 
 
 
 
 
 
5520-B-800 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Triathlon 
Symmetric 
Conventional 
Polyethylene 
Patella 
 
Triathlon 
Symmetric X3 
Patella 
 
Triathlon 
Asymmetric 
Conventional 
Polyethylene 
Patella 
 
Triathlon 
Asymmetric X3 
Patella 
5550-L-278 
 
5550-G-278 
 
5551-L-299 
 
5551-G-299 
5550-L-298 
 
5550-G-298 
 
5551-L-320 
 
5551-G-320 
5550-L-319 
 
5550-G-319 
 
5551-L-350 
 
5551-G-350 
5550-L-339 
 
5550-G-339 
 
5551-L-381 
 
5551-G-381 
5550-L-360 
 
5550-G-360 
 
5551-L-401 
 
5551-G-401 
 
 
5550-G-278-E 
 
 
 
5551-G-299-E 
 
 
5550-G-298-E 
 
 
 
5551-G-320-E 
 
 
5550-G-319-E 
 
 
 
5551-G-350-E 
 
 
5550-G-339-E 
 
 
 
5551-G-381-E 
 
 
5550-G-360-E 
 
 
 
5551-G-401-E 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Triathlon CR 
Cemented Femur 
 
Triathlon PS 
Cemented Femur 
 
Triathlon CR 
Conventional 
Polyethylene 
Tibial Inserts 
 
Triathlon CR X3 
Tibial Inserts 
5510-F-101 
 
5515-F-101 
 
5530-P-X09 
 
5530-G-X09 
5510-F-102 
 
5515-F-102 
 
5530-P-X10 
 
5530-G-X09-E 
5510-F-201 
 
5515-F-201 
 
5530-P-X11 
 
5530-G-X10-E 
5510-F-202 
 
5515-F-202 
 
5530-P-X12 
 
5530-G-X11 
5510-F-301 
 
5515-F-301 
 
5530-P-X13 
 
5530-G-X11-E 
5510-F-302 
 
5515-F-302 
 
5530-P-X14 
 
5530-G-X12-E 
5510-F-401 
 
5515-F-401 
 
5530-P-X16 
 
5530-G-X13 
5510-F-402 
 
5515-F-402 
 
5530-P-X19 
 
5530-G-X13-E 
5510-F-501 
 
5515-F-501 
 
 
 
5530-G-X14-E 
5510-F-601 
 
5515-F-601 
 
 
 
5530-G-X16 
5510-F-701 
 
5515-F-701 
 
 
 
5530-G-X16-E 
5510-F-801 
 
5515-F-801 
 
 
 
5530-G-X19 
5510-F-802 
 
5515-F-802 
 
 
 
5530-G-X19-E 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Triathlon CS 
Conventional 
Polyethylene Tibial 
Inserts 
 
Triathlon CS X3 
Tibial Inserts 
 
Triathlon PS 
Conventional 
Polyethylene 
Tibial Inserts 
 
Triathlon PS X3 
Tibial Inserts 
5531-P-X09 
 
5531-G-X09 
 
5532-P-X09 
 
5532-G-X09 
5531-P-X10 
 
5531-G-X09-E 
 
5532-P-X10 
 
5532-G-X09-E 
5531-P-X11 
 
5531-G-X10-E 
 
5532-P-X11 
 
5532-G-X10-E 
5531-P-X12 
 
5531-G-X11 
 
5532-P-X12 
 
5532-G-X11 
5531-P-X13 
 
5531-G-X11-E 
 
5532-P-X13 
 
5532-G-X11-E 
5531-P-X14 
 
5531-G-X12-E 
 
5532-P-X14 
 
5532-G-X12-E 
5531-P-X16 
 
5531-G-X13 
 
5532-P-X16 
 
5532-G-X13 
5531-P-X19 
 
5531-G-X13-E 
 
5532-P-X19 
 
5532-G-X13-E 
5531-P-X22 
 
5531-G-X14-E 
 
5532-P-X22 
 
5532-G-X14-E 
 
 
5531-G-X16 
 
 
 
5532-G-X16 
 
 
5531-G-X16-E 
 
 
 
5532-G-X16-E 
 
 
5531-G-X19 
 
 
 
5532-G-X19 
 
 
5531-G-X19-E 
 
 
 
5532-G-X19-E 
 
 
5531-G-X22-E 
 
 
 
5532-G-X22-E 
 
 
5531-G-X25 
 
 
 
5532-G-X25 
X= size 1,2,3,4,5,6,7 and 8 
 
 
  
 
 
 

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Appendix B Case Report Forms 
 
 
Title page 
 

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Appendix C 510k Clearance Letters 
1. Simplex HV 
 

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2. Simplex HV Gentamicin 
 
 
 

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Appendix D Instructions for Use 
1. Simplex HV 
 
 
 
 

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2. Simplex HV Gentamicin 
 
 

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