NexGen® TM Tibia Clinical Outcomes Study: Prospective Multicenter Study of the NexGen® TM Monoblock and Modular Tibias
Phase: NA
Conditions: Osteoarthritis, Rheumatoid Arthritis, Traumatic Arthritis, Polyarthritis, Collagen Disorders and/or Avascular Necrosis of the Femoral Condyle, Post-traumatic Loss of Joint Configuration, Moderate Valgus, Varus, or Flexion Deformities
Sponsor: Zimmer Biomet

 
 
 
 
NexGen® TM Tibia 
Clinical Outcomes Study 
 
PROSPECTIVE MULTICENTER STUDY  
OF THE 
NexGen® TM Monoblock and Modular Tibias 
 
Protocol #K.CR.I.G.16.34 
U.S. 
 
 
July 17, 2017 – Version 1.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY SPONSOR 
Zimmer, Inc. 
Clinical Affairs Department 
1800 West Center Street 
Warsaw, IN 46580 
800-613-6131 
 
 
CONFIDENTIAL - This document contains confidential information belonging to Zimmer Inc. except as otherwise 
agreed to in writing, by accepting or reviewing this document, you agree to hold this information in confidence and 
not distribute or disclose it to others (except where required by  applicable law) or use it for unauthorized 
purposes.  In the event of any actual or suspected breach of this obligation, Zimmer Inc. must be promptly notified.  
Duplication and distribution of this document in any form or shape requires prior approval from Zimmer Inc. 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 2 of 25 
 
Table of Contents 
 
 
Document History ............................................................................................................................. 3 
I.
 
Study Synopsis .................................................................................................................................. 4 
II.
 
Data Collection Overview .................................................................................................................. 7 
III.
 
Introduction and Purpose ................................................................................................................. 8 
IV.
 
Study Objectives................................................................................................................................ 8 
V.
 
Study Design ...................................................................................................................................... 8 
VI.
 
Study Population ............................................................................................................................... 9 
VII.
A. 
Inclusion Criteria ............................................................................................................................... 9 
B. 
Exclusion Criteria ............................................................................................................................. 10 
 
Study Device Information ............................................................................................................... 10 
VIII.
 
Study Procedures ............................................................................................................................ 10 
IX.
A. 
Offer Study Participation................................................................................................................. 10 
B. 
Informed Consent Process .............................................................................................................. 11 
C. 
Subject Enrollment .......................................................................................................................... 11 
D. 
Subject Enrollment Log ................................................................................................................... 11 
E. 
Monitor Log ..................................................................................................................................... 12 
F. 
Delegation of Authority .................................................................................................................. 12 
G. 
Preoperative Data Collection .......................................................................................................... 12 
H. 
Surgical Technique .......................................................................................................................... 12 
I. 
Surgical and Immediate Post-Surgical Data Collection ................................................................... 12 
J. 
Postoperative Follow-up Data Collection ....................................................................................... 13 
K. 
Minimization of Subjects Lost to Follow-up .................................................................................... 13 
L. 
Radiographic Definitions and Methods .......................................................................................... 13 
M. Recommended Revision Procedure ................................................................................................ 14 
 
Reporting......................................................................................................................................... 14 
X.
A. 
Prior to Initiation of the Study ........................................................................................................ 15 
B. 
Clinical Data Collection/Submission ................................................................................................ 15 
C. 
Reporting Requirements ................................................................................................................. 16 
D. 
Management of Incurrent Events ................................................................................................... 16 
E. 
Medical Events/Adverse Events Definitions and Classifications ..................................................... 19 
F. 
Monitoring of the Study .................................................................................................................. 22 
 
Risk Analysis .................................................................................................................................... 22 
XI.
A. 
General Surgical Risks ..................................................................................................................... 23 
B. 
Risks Associated with Cementless Total Knee Arthroplasty/Study Device ..................................... 23 
 
Statistical Considerations ................................................................................................................ 24 
XII.
A. 
General Statistical Methods ............................................................................................................ 24 
B. 
Sample Size ..................................................................................................................................... 24 
 
References....................................................................................................................................... 25 
XIII.
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 3 of 25 
 
Appendices: 
 
Appendix A 
Sample Informed Consent 
Appendix B 
Source Documents (Case Report Forms) 
Appendix C 
Study Logs 
Appendix D 
Radiographic Protocol 
Appendix E 
Medical Device Reporting Information Form (MDRIF) 
Appendix F 
Explant Procedure 
Appendix G 
Study Abbreviations 
 
 
Document History 
I.
 
Version 
Date 
Description of Change 
Author/Revised By 
1.0 
17-JUL-2017 
Initial Document 
Scott Abshagen 
 
 
 
 
 
 
 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 4 of 25 
 
 
Study Synopsis  
II.
 
STUDY TITLE 
NexGen® TM Tibia Clinical Outcomes Study 
SPONSOR 
Zimmer Inc., Warsaw, Indiana 
PROTOCOL #  
K.CR.I.AM.16.34 
STUDY DEVICES 
 
Zimmer TMT: NexGen® Trabecular Metal Monoblock Tibias 
(referenced as NexGen TM Monoblock Tibia throughout protocol) 
 
Zimmer, Inc: NexGen® Trabecular Metal Tibial Trays   
(referenced as NexGen TM Modular Tibia throughout protocol) 
 
Cementless tibias used with the NexGen® Knee System or Persona® femoral. 
STUDY 
OBJECTIVE 
The objective of this study is to evaluate clinical performance for the 
commercially available NexGen TM Monoblock Tibia and NexGen TM Modular 
Tibia used in primary cementless tibia total knee arthroplasty. 
 
The assessments will include: 
1. Clinical performance measured by radiographic parameters, pain and 
function, and survival of the device. 
2. Safety based on incidence and frequency of adverse events. 
ENDPOINTS 
Primary Endpoint: 
The primary endpoint of this study is to evaluate the clinical performance of the 
implant at 2 years postoperatively using radiographic parameters.  Radiographs 
will be assessed for the absence of progressive tibial radiolucencies, as defined in 
the radiographic protocol. 
 
Secondary Endpoints: 
The secondary endpoints of this study will evaluate the clinical performance of 
the implant at 2 years postoperatively, based upon: 
 
No revisions for any reason 
 
Oxford Knee Score (OKS) >38 
TARGET 
POPULATION 
Patients qualifying for primary cementless tibia total knee arthroplasty who meet 
the inclusion/exclusion criteria for study participation. 
STUDY DESIGN 
Prospective, multicenter, non-randomized, non-controlled  
STUDY TYPE 
Post Market Outcomes Study 
SAMPLE SIZE 
A minimum of 132 subjects are to be enrolled in this study. 
 
Approximate equal distribution with at least 66 NexGen TM Monoblock 
and 66 NexGen TM Modular subjects.   
 
Up to 10 U.S. sites, each contributing between 22 to 30 subjects.  
 
Each site will be selected for a specific NexGen TM device, either the 
Monoblock or Modular design.   
 
The NexGen TM Monoblock Tibia and NexGen TM Modular Tibia are 
considered 2 single-arms being analyzed separately. 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 5 of 25 
 
LENGTH OF 
STUDY 
4 years (6 months enrollment, 2 years follow-up, and interval windows) 
 
Enrollment/Preoperative 
 
Immediate Postop Radiograph (Pre weight-bearing) 
 
6 weeks (± 2 weeks) 
 
6 months (± 1 month) 
 
1 year (± 1 month) 
 
2 years (± 2 months) 
SCORES 
Forgotten Joint Score (FJS-12) 
Oxford Knee Score (OKS) 
UCLA Activity & Satisfaction Survey 
RADIOGRAPHS 
AP and Lateral X-rays will be required of the operative knee immediate postop 
and at each clinical follow-up visit.  Radiographs will be reviewed for image 
quality by the surgeon during the subject’s clinical visit.  Radiographic images 
must show an orthogonal view of the tibial implant interface.   
 
Study radiographs will be requested from sites for independent radiographic 
review. 
INCLUSION 
CRITERIA 
 
INCLUSION CRITERIA: 
1. Patient is at least 18 years of age. 
2. Patient qualifies for a primary cementless tibia total knee arthroplasty based 
on physical exam and medical history, including diagnosis of severe knee pain 
and disability due to at least one of the following: 
a. Rheumatoid arthritis, osteoarthritis, traumatic arthritis, polyarthritis. 
b. Collagen disorders and/or avascular necrosis of the femoral condyle. 
c. Post-traumatic loss of joint configuration, particularly when there is 
patellofemoral erosion, dysfunction or prior patellectomy. 
d. Moderate valgus, varus, or flexion deformities. 
e. The salvage of previously failed surgical attempts that did not include 
partial or total knee arthroplasty of the ipsilateral knee. 
3. Patient has participated in the study-related Informed Consent process. 
4. Patient is willing and able to provide written Informed Consent by signing and 
dating the IRB approved Informed Consent Form. 
5. Patient is willing and able to complete scheduled study procedures and 
follow-up evaluations as described in the Informed Consent Form. 
6. Independent of study participation, patient is a candidate for commercially 
available cementless NexGen TM tibial knee component, implanted in 
accordance with product labeling. 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 6 of 25 
 
EXCLUSION 
CRITERIA 
 
EXCLUSION CRITERIA: 
1. Previous history of infection in the affected joint. 
2. Active local or systemic infection that may affect the prosthetic joint. 
3. Insufficient bone stock on femoral or tibial surfaces. 
4. Skeletal immaturity. 
5. Neuropathic arthropathy. 
6. Osteoporosis or any loss of musculature or neuromuscular disease that 
compromises the affected limb. 
7. A stable, painless arthrodesis in a satisfactory functional position. 
8. Severe instability secondary to the absence of collateral ligament integrity. 
9. Rheumatoid arthritis accompanied by an ulcer of the skin or a history of 
recurrent breakdown of the skin. 
10. Patient has previously received partial or total knee arthroplasty for the 
ipsilateral knee. 
11. Patient is currently participating in any other surgical intervention studies or 
pain management studies. 
12. Patient is known to be pregnant or considered a member of a protected 
population (e.g., prisoner, mentally incompetent, etc.). 
13. Patient has a known or suspected sensitivity or allergy to one or more of the 
implant materials. 
STATISTICAL 
REPORTING 
Clinical performance will be evaluated for radiographic success, pain and 
function, and implant survival by summarizing the data descriptively.  Categorical 
data (e.g., gender, component size) will be reported using frequency and 
percentages with 95% Confidence Interval (CI) over the time periods of interest.  
Continuous data (e.g. age, weight) will be summarized using mean, standard 
deviation, minimum, median, maximum, and 95% CI over the time periods of 
interest.  Implant survival will be summarized using a Kaplan-Meier method and 
presented with rates (expressed as percentages) and CI.  Routine summaries of 
complication data will be in the form of frequencies and percentages. 
 
This protocol is written based on guidelines from ISO 14155:2011 Standard for Clinical Investigation of 
Medical Devices For Human Subjects – Good Clinical Practice [1] and is in accordance with US Code of 
Federal Regulations 21 CFR Parts 11, 50 and 56 [2]. 
 
 
 
 
 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 7 of 25 
 
 
Data Collection Overview 
III.
The following tables indicate required forms and activities to be completed at the given time 
point: 
 
Form Name 
Preop 
Surgical to 
Immediate 
Postop 
6 Weeks 
Postop  
 (± 2 weeks ) 
 6 Months 
Postop  
 (± 1 month) 
1 Year 
Postop 
(± 1 month) 
2 Years 
Postop 
(± 2 months) 
Site and Subject completed: 
Informed Consent Form 
X 
 
 
 
 
 
Site completed: 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
Demographic Evaluation 
X 
 
 
 
 
 
Surgical & Discharge Information 
 
X 
 
 
 
 
Physical Exam 
X 
 
X 
X 
X 
X 
Physician Assessment of Postop 
Radiographs 
 
X 
X 
X 
X 
X 
Subject completed:
Forgotten Joint Score (FJS-12) 

 




Oxford Knee Score (OKS) 

 




UCLA Activity & Satisfaction 
Survey 

 




Site completed as applicable:
Adverse Event Report 
 
 
 



Protocol Deviation 
 
 
 



Study Completion 
 
 
 



Explanted Device Form  






 
Activity 
Preop 
Immediate 
Postop 
6 Weeks 
Postop 
6 Months 
Postop 
1 Year 
Postop 
2 Years 
Postop 
Radiograph Submission 
 
X 
X 
X 
X 
X 
 
 
 
 
 
The following table indicates required forms to be completed by the site for revision patients: 
 
Form Name 
Comments 
Physician Assessment of Postop Radiographs 
Mark the “Pre-Revision” exam period. 
Adverse Event Report 
Document adverse event resulting in the revision. 
Study Completion 
Complete indicating “Study Prosthesis Removed” under Study 
Completion Status. 
Explanted Device Form 
Document explanted device information.  Send explanted device to 
Zimmer Biomet per Appendix F. 
Medical Device Reporting Information  Form 
(MDRIF): 
 
If device-related, complete MDRIF form (Appendix E) and forward the 
form and all applicable supporting documents to Zimmer Biomet 
within 7 days. The supporting documents include: 
 Operative reports (index and revision surgery) 
 Radiographs (immediate postop, intermediate, and pre-revision) 
X 
Site completed (Investigator or designee) 
 Subject completed 
 Site completed as applicable (Investigator or designee) 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 8 of 25 
 
 
Introduction and Purpose 
IV.
In recent years the advent of highly porous trabecular metal implants in cementless fixation has 
brought the cemented vs. cementless debate back to the forefront among surgeons when 
determining best practices and benefits to patients.  Fricka, et al [3], describe the potential 
benefits of cementless fixation as preservation of bone stock, shorter operating room time (and 
thus a cost savings), ease of revision if necessary, and elimination of any complications 
associated with cemented fixation such as third body wear and retained loose fragments.  
Potential disadvantages are the lack of surgeon experience implanting the modular tibial tray, 
cost of such implants, and determining if there is an ideal patient population for implantation of 
such devices.   
 
To address clinical challenges and methodologically address implant characteristics, a 
prospective, multi-center, longitudinal data collection model is being proposed for NexGen TM 
Tibia components used in primary cementless tibia total knee arthroplasty.  
 
Study Objectives 
V.
The primary objective of this study is to evaluate clinical performance for the commercially 
available NexGen TM Monoblock Tibia and NexGen TM Modular Tibia used in primary 
cementless tibia total knee arthroplasty.  This will be done by analysis of radiographic 
parameters and validated patient report outcome measurements as well as monitoring adverse 
events and survivorship of the implant.   
 
The assessments will include: 
1. Clinical performance measured by radiographic parameters, pain and function, and 
survival of the device. 
2. Safety based on incidence and frequency of adverse events. 
 
 
Study Design 
VI.
This is a prospective, multicenter, non-randomized clinical study designed to facilitate the 
collection and evaluation of radiographic parameters, pain and function, survival of the device, 
and adverse event data.  This clinical study will include the NexGen TM Monoblock Tibia and 
NexGen TM Modular Tibia as 2 single-arms being analyzed separately.  
 
The primary endpoint of this study is to evaluate the clinical performance of the implant at 2 
years postoperatively using radiographic parameters.  Radiographs will be assessed for the 
absence of progressive tibial radiolucencies, as defined in the radiographic protocol. 
 
The secondary endpoints of this study will evaluate the clinical performance of the implant at 2 
years postoperatively, based upon: 
• 
No revisions for any reason 
• 
Oxford Knee Score >38 
 
A minimum of 132 subjects are to be enrolled in this study, with approximate equal distribution 
of at least 66 NexGen TM Monoblock and 66 NexGen TM Modular subjects.  A maximum of 10 
U.S. sites will contribute, each enrolling between 22 to 30 implanted knees.  Each site will be 
selected for a specific NexGen TM device, either the Monoblock or Modular design.  

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 9 of 25 
 
Investigators will be skilled in cementless total knee arthroplasty and experienced implanting 
either the NexGen TM Monoblock Tibia or the NexGen TM Modular Tibia. 
 
Each Principal Investigator will be responsible for obtaining Institutional Review Board (IRB) 
approval as required prior to conducting the study.  In order to avoid potential selection bias, 
each Investigator will offer study participation to each consecutive eligible patient presenting as 
a candidate for primary cementless tibia total knee arthroplasty using the NexGen TM 
Monoblock or NexGen TM Modular Tibia.  Eligible candidates who express interest in study 
participation will be offered Informed Consent.  All potential study subjects will be required to 
participate in the Informed Consent process and will not be considered enrolled in the study 
until the candidate has signed and dated the IRB approved Informed Consent Form.  Study data 
cannot be collected until the candidate has completed the Informed Consent process and 
signed and dated the IRB approved Informed Consent Form. 
 
All study subjects will undergo preoperative clinical evaluations prior to their cementless tibia 
total knee arthroplasty.   An immediate postoperative radiograph will be required.  Postoperative 
clinical follow-up and radiographic evaluations will be conducted at 6 weeks, 6 months, 1 year, and 
2 years.    
 
The Investigator will review radiographs immediately postop and at each clinical evaluation to 
ensure the radiographs meet the protocol requirements.  The Sponsor will provide a 
radiographic protocol (Appendix D) to assist sites in proper x-ray technique in order to assure 
adequate images are captured for study analysis.   
 
The Sponsor will request copies of these radiographs for independent radiologic review.  The 
Sponsor will request one central reviewer for all radiographs independent of the surgeon and 
institution. 
 
 
Study Population 
VII.
The study population for primary statistical analysis will be comprised of subjects who require 
primary cementless tibia total knee arthroplasty and satisfy the inclusion/exclusion criteria 
outlined in this section of the protocol.  In order to avoid potential selection bias, Investigators 
will offer study participation to each consecutive eligible patient presenting as a candidate for 
primary cementless tibia total knee arthroplasty using the commercially available NexGen TM 
Monoblock or NexGen TM Modular Tibia implants.  Eligible candidates who express interest in 
study participation will be offered Informed Consent.  The Inclusion/Exclusion Criteria should 
not be completed until the study-specific Informed Consent Form has been completed.  
A. Inclusion Criteria 
1. Patient is at least 18 years of age. 
2. Patient qualifies for a primary cementless tibia total knee arthroplasty based on 
physical exam and medical history, including diagnosis of severe knee pain and 
disability due to at least one of the following: 
a. Rheumatoid arthritis, osteoarthritis, traumatic arthritis, polyarthritis. 
b. Collagen disorders and/or avascular necrosis of the femoral condyle. 
c. Post-traumatic loss of joint configuration, particularly when there is patellofemoral 
erosion, dysfunction or prior patellectomy. 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 10 of 25 
 
d. Moderate valgus, varus, or flexion deformities. 
e. The salvage of previously failed surgical attempts that did not include partial or 
total knee arthroplasty of the ipsilateral knee. 
3. Patient has participated in the study-related Informed Consent process. 
4. Patient is willing and able to provide written Informed Consent by signing and dating 
the IRB approved Informed Consent Form. 
5. Patient is willing and able to complete scheduled study procedures and follow-up 
evaluations as described in the Informed Consent Form. 
6. Independent of study participation, patient is a candidate for commercially available 
cementless NexGen TM tibial knee component, implanted in accordance with product 
labeling. 
B. Exclusion Criteria 
1. Previous history of infection in the affected joint. 
2. Active local or systemic infection that may affect the prosthetic joint. 
3. Insufficient bone stock on femoral or tibial surfaces. 
4. Skeletal immaturity. 
5. Neuropathic arthropathy. 
6. Osteoporosis or any loss of musculature or neuromuscular disease that compromises 
the affected limb. 
7. A stable, painless arthrodesis in a satisfactory functional position. 
8. Severe instability secondary to the absence of collateral ligament integrity. 
9. Rheumatoid arthritis accompanied by an ulcer of the skin or a history of recurrent 
breakdown of the skin. 
10. Patient has previously received partial or total knee arthroplasty for the ipsilateral 
knee. 
11. Patient is currently participating in any other surgical intervention studies or pain 
management studies. 
12. Patient is known to be pregnant or considered a member of a protected population 
(e.g., prisoner, mentally incompetent, etc.). 
13. Patient has a known or suspected sensitivity or allergy to one or more of the implant 
materials. 
 
 Study Device Information 
VIII.
NexGen knee components included in this study are the NexGen TM Monoblock Tibia or NexGen 
TM Modular Tibia.   Both the NexGen TM Tibias are designed specifically to adhere to bone 
through the use of trabecular metal technology.  These devices are intended for long-term 
implantation in accordance with product labeling.  Please refer to the package insert for 
additional information and instructions. 
 
 
Study Procedures 
IX.
A. Offer Study Participation 
Study participation will be offered to each consecutive eligible patient presenting as a potential 
candidate for primary cementless tibia total knee arthroplasty using the commercially available 
NexGen TM Monoblock or NexGen TM Modular Tibia implants, depending on the clinical site’s 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 11 of 25 
 
device designation.  A Subject Enrollment Log (Appendix C) will be completed to document all 
individuals screened as potential candidates for the study.  Eligible candidates who express 
interest in study participation will be offered Informed Consent.  Prior to patient involvement in 
the study, the patient must participate in the Informed Consent process and sign and date the 
IRB approved Informed Consent Form. 
B. Informed Consent Process 
For candidates that express interest, the Investigator or Designee will describe relevant study 
information, including the purpose, procedures, possible risks, and potential benefits associated 
with study participation.  The Investigator or Designee will also review, along with the candidates, 
the Informed Consent Form approved by both the governing IRB and the study Sponsor.  
Candidates shall have sufficient time to read and understand the IRB approved Informed Consent 
Form and discuss whether they wish to participate in the study.  Candidates will be asked to 
acknowledge whether all of their questions and concerns have been addressed to their 
satisfaction.  Any questions that candidates may have will be addressed appropriately by the 
Investigator or Designee.  Candidates will be further instructed that they are free to obtain 
additional information from the Investigator or Designee at any time, that they are free to decline 
participation, and that they are free to withdraw their consent and discontinue their participation 
at any time without prejudice. 
 
After completing the Informed Consent process, candidates who agree to enter the study must 
sign and date the IRB approved Informed Consent Form.  The Informed Consent Form must be 
signed and dated prior to study data collection and the date of study surgery.  For bilateral TKA 
candidates that agree to enroll for both operative sides, a separate Informed Consent Form must 
be signed and dated for each operative side.  
 
A copy of the signed Informed Consent Form should be provided to the subject.  The original 
signed Informed Consent Form is to be filed in the subject’s study binder. 
 
Study data will not be collected until the Informed Consent Form has been signed and dated.  If 
the candidate does not wish to participate (does not sign and date the Informed Consent Form), 
data for that candidate will not be collected for this study. 
C. Subject Enrollment 
Once the Informed Consent Form has been signed and dated by the subject, the subject will be 
considered enrolled in the study.  A unique case identification number (Case ID) will be assigned 
to each participating subject/knee (bilateral subjects will be assigned a unique case ID number for 
each knee).  This unique case ID number will be used throughout the study for identification.  
Case ID numbers will be assigned consecutively in ascending order per site, with the starting 
number for a given site defined by the Sponsor.    
 
The subject will be considered an active study subject after receiving the study device during 
surgery.  In the event that a subject does not receive the study device at the time of surgery, a 
Study Completion form must be submitted and this will be documented as a screen failure. 
D. Subject Enrollment Log 
A Subject Enrollment Log (Appendix C) will be maintained at the site throughout the course of 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 12 of 25 
 
the study and filed in the site Regulatory Binder.  The purpose of the log is to provide 
documentation that all enrolled study subjects underwent the Informed Consent process.  All 
candidates who sign and date the approved Informed Consent Form for the study must be 
entered in the log.  If a subject signs and dates additional Informed Consent Form(s) after 
enrollment (e.g., due to a protocol amendment, protocol revisions, etc.), subsequent signings will 
also be recorded in the log.  The proposed date of surgery for each subject will also be added to 
the log.      
E. Monitor Log 
The Monitoring Visit Log (Appendix C) will be maintained throughout the course of the study.  
The log will contain the visit date, monitor name/signature and the purpose of the visit (i.e. site 
initiation, onsite interim monitoring, site close-out, etc.).  The monitoring visit log will be filed in 
the site Regulatory Binder for the study. 
F. Delegation of Authority 
A Delegation of Authority Log (Appendix C) will be maintained throughout the study and will 
contain the names, initials, signatures and study responsibilities of all site personnel/designees 
involved in study procedures and data collection.  The Delegation of Authority Log will be filed in 
the site Regulatory Binder for the study. 
G. Preoperative Data Collection 
Preoperative data will be collected on the following source documents: 
1. Inclusion/Exclusion Criteria 
2. Demographic Evaluation 
3. Physical Exam 
4. Forgotten Joint Score (FJS-12) 
5. Oxford Knee Score 
6. UCLA Activity & Satisfaction Survey 
7. Protocol Deviation (as applicable) 
8. Study Completion (as applicable) 
H. Surgical Technique 
Standard operative procedures will be followed and all surgical procedures will be performed 
under aseptic conditions.  Investigators will implant all commercially available NexGen TM Tibia 
implants and any other compatible products in compliance with corresponding labeling 
requirements and in accordance with appropriate surgical technique(s), found on 
www.zimmerbiomet.com.  NexGen TM Tibia implants in this study must be implanted 
cementless, without the use of autograft bone paste slurry. 
I. 
Surgical and Immediate Post-Surgical Data Collection 
Surgical and immediate post-surgical data will be collected on the following source documents: 
1. Surgical & Discharge Information 
2. Physician Assessment of Postop Radiographs 
3. Adverse Event Report (as applicable) 
4. Protocol Deviation (as applicable) 
5. Study Completion (as applicable) 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 13 of 25 
 
Post-surgical management for study subjects will follow the investigator’s standard of care for 
patients undergoing total knee arthroplasty (e.g. prophylactic antibiotic therapy, prevention of 
deep vein thrombosis, prevention of pulmonary embolism, etc.).  Post-surgical rehabilitative 
therapy will be as prescribed by the investigator. 
J. Postoperative Follow-up Data Collection 
Postoperative follow-up clinical evaluations will be conducted at the following visit intervals: 
 
Clinical Interval 
Interval Window in 
Days Postop* 
Approximate Window in 
Weeks or Months Postop 
6 weeks 
28 to 56 days 
± 2 weeks 
6 months 
151 to 214 days 
± 1 month 
1 year 
333 to 396 days 
± 1 month 
2 years 
669 to 791 days 
± 2 months 
*Visit(s) outside of window will be determined based on Days Postop 
 
Postoperative follow-up clinical data will be collected on the following source document forms: 
1. Physical Exam 
2. Physician Assessment of Postop Radiographs 
3. Forgotten Joint Score 
4. Oxford Knee Score 
5. UCLA Activity & Satisfaction Survey 
6. Adverse Event Report (as applicable) 
7. Protocol Deviation (as applicable) 
8. Study Completion (as applicable) 
9. Explanted Device Form (as applicable) 
 
Subjects will be followed postoperatively for 2 years.  Unless the study is otherwise closed, data 
will continue to be collected until the subject completes the study per the protocol, voluntarily 
withdraws from the study, is withdrawn from the study by the investigator, is lost to follow-up, 
undergoes revision to remove a study device, or expires.  See Management of Incurrent Events 
(Section X, Subsection D of this protocol) for additional details.  Reason(s) for study completion 
must be documented on the Study Completion form.   
K. Minimization of Subjects Lost to Follow-up 
Subject follow-up is extremely important for the conduct of a clinical study, and the expectation 
is to maintain the highest possible rate of follow-up compliance throughout this study.  During 
the informed consent process and at each follow-up interval, subjects should be counseled on 
the importance of completing future study follow-up intervals. 
L. Radiographic Definitions and Methods 
All postoperative radiographs will be evaluated by the Investigator and documented using the 
Physician Assessment of Postop Radiographs.  An Adverse Event Report must be completed for 
findings identified as an adverse event.   
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 14 of 25 
 
It is the Investigator’s responsibility to review radiographs for image quality during the subject’s 
clinical visit and prior to uploading into the image collection service.  Radiographic images must 
show an orthogonal view of the tibial implant interface.  If the Sponsor determines a radiograph 
is of poor quality, then the site must reschedule the subject for additional radiographs.   
 
1. Required radiographic views 
 
Radiographic Interval 
Interval Window 
Required Radiograph 
Immediate Postop 
Pre weight-bearing 
AP and Lateral 
6 weeks 
± 2 weeks 
AP and Lateral 
6 months 
± 1 month 
AP and Lateral 
1 year 
± 1 month 
AP and Lateral 
2 years 
± 2 months 
AP and Lateral 
 
Both Anteroposterior (AP) and Lateral radiographs are required of the operative knee.  
These images should be taken according to the radiographic protocol (Appendix D).  
Radiographs should have similar exposure and must show the entire study device and 
surrounding bone.  The investigative site will retain copies (hard copy/CD/digital) of all 
radiographs referenced for the study. 
 
Immediate Postop Radiographs: 
Fluoroscopic imaging is the optimal technique for immediate postop radiographs 
taken in the Operating Room.  Standard films that show an orthogonal view of the 
tibial implant interface and taken prior to weight-bearing will also be accepted.    
 
Follow-up Radiographs: 
Required intervals include clinical follow-up visits at 6 weeks, 6 months, 1 year, and 2 
years.  Images must show an orthogonal view of the tibial implant interface.   
 
2. Submission to Sponsor 
All radiographs must be submitted to Sponsor via the designated image collection 
services.  Postoperative study radiographs will be assessed by an independent 
radiographic reviewer. 
M. Recommended Revision Procedure 
See Management of Incurrent Events (Section X, Subsection D of this protocol) 
 
 
Reporting 
X.
The management of all study data received by the Sponsor will be the responsibility of the 
Sponsor or its Designee.  The use or disclosure of all protected health information will comply 
with the Health Insurance Portability and Accountability Act (HIPAA).  All information will be 
treated with strict adherence to professional standards of confidentiality and will be filed by the 
Sponsor under adequate security and restricted accessibility by clinical personnel.  All electronic 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 15 of 25 
 
systems used to create, modify, maintain, or transmit study records will be validated according to 
21 CFR Part 11 [2].  Reports and communications relating to study subjects will typically identify 
each subject only by the subject’s initials, assigned study subject Case ID number, date of 
surgery, operative side, and date of birth.  This code must be clearly linked to the patient identity 
and can only be decoded by the study center. 
A. Prior to Initiation of the Study 
1. Clinical Trial Agreement (CTA) 
A fully executed (signed by all required parties) CTA must be on file with the Sponsor 
prior to any investigator participating in this study. 
 
2. Institutional Review Board Protocol Approval 
This study protocol must be submitted to and approved by the Investigator’s 
Institutional Review Board (IRB).  A copy of the IRB approval letter must be submitted 
to Sponsor.   The letter should identify the following: 
 
Protocol name and/or number 
 
Date of IRB meeting (if available)  
 
Date of approval 
 
Date of expiration 
 
Signature of IRB  
 
3. Informed Consent 
A Sponsor-approved sample Informed Consent Form (Appendix A) will be provided 
along with the study protocol for IRB submission and approval.  If the IRB requires 
revisions to the provided Informed Consent Form, the requested revisions must be 
submitted by the Investigator to the Sponsor for review and approval.  Once the 
Sponsor has reviewed and approved the revision, the Informed Consent Form will be re-
submitted to the IRB for final review and approval.  A copy of the final IRB approved 
Informed Consent Form (ICF) must be submitted to Sponsor. 
 
4. ClinicalTrials.gov Registration 
The Sponsor will be responsible for registering this study on www.ClinicalTrials.gov. 
B. Clinical Data Collection/Submission 
1. Summary of Source Document Data Collection 
Study data will be collected on source documents, which may include study-specific 
documents provided by the Sponsor.  For subjects having bilateral knee replacement, 
separate source documents must be completed for each operative side. 
 
The following source document completion guidelines should be followed: 
 
Complete carefully and accurately. 
 
Complete header information consistently across all source documents for 
each individual study subject (when study-specific forms are used). 
 
Be sure that data on the source documents match that which is entered 
through the electronic data capture (EDC) system. 
 
Use the study subject’s unique Case ID number assigned as instructed.  Do 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 16 of 25 
 
not provide information that is not requested on the source documents. 
 
Ensure that all fields are completed.  For fields completed by the subject, 
efforts should be made to obtain any missing responses prior to the subject 
completing their visit. 
 
2. Data Submission 
Completed source documents will be submitted directly to Sponsor by electronic data 
capture (EDC) and submission via a method approved by Sponsor.  Every effort must be 
made to ensure data submission to Sponsor is made within 14 days of the visit 
completion. 
 
3. Quality Assurance of Data 
The Investigator should ensure the accuracy, completeness, legibility, and timeliness of 
the data reported to the Sponsor in the EDC and in all required reports.  Data reported 
in EDC, which are derived from source documents, should be consistent with the source 
documents or the discrepancies should be explained.  All electronic systems used to 
create, modify, maintain, or transmit electronic study records will be validated 
according to 21 CFR Part 11 [2].  The Sponsor will maintain quality control systems, in 
accordance with the Sponsor’s policies and procedures. 
C. Reporting Requirements 
1. Investigator Reporting Responsibilities 
The Investigator should ensure the accuracy, completeness, legibility, and timeliness of 
data reported to the Sponsor in accordance with this protocol.  The Investigator or 
Designee will provide periodic reports to their IRB as required to maintain IRB approval 
throughout the study, and will provide any required final reporting to the IRB upon 
study completion/termination.  A copy of all IRB re-approval letters must be submitted 
to the Sponsor.  If the IRB terminates or suspends its approval of the study, the 
Investigator or Designee will suspend study-related activities and will promptly notify 
the Sponsor.  The Investigator should also promptly provide written reports to the 
Sponsor and the IRB regarding any changes significantly affecting the conduct of the 
study, and/or increasing risk to the subjects. 
 
2. Retention of Records 
Study records must be retained by the Investigator or Designee for a minimum of 2 
years from the Investigator’s study termination date, or per applicable regulatory 
and/or IRB requirements (whichever time period is greater).  Measures shall be taken to 
prevent accidental or premature destruction. 
D. Management of Incurrent Events 
1. Failure to Obtain Informed Consent 
Study data will not be collected until the Informed Consent Form has been properly 
executed.  If a candidate does not wish to participate (does not sign and date the 
Informed Consent Form), data for that candidate will not be collected for this study. 
 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 17 of 25 
 
2. Reporting and Documentation of  Medical Events, Adverse Events and Adverse Device 
Effects 
Adverse Events, Serious Adverse Events, Adverse Device Effects, and Serious Adverse 
Device Effects will be documented on the Adverse Event Report throughout this study, 
including information on the date of onset, treatment and resolution, as well as 
assessment of both the seriousness and the relationship to the study device.  The 
outcome of complications will be documented and changes in outcome are to be 
updated during the course of the study.  In case of early termination of this study, 
further follow-up of the subject shall proceed according to the hospital’s standard 
procedure. 
 
Device Deficiencies that did not lead to an adverse event but could have led to a 
medical occurrence if suitable actions had not been taken, if intervention had not been 
made, or if circumstances had been less fortunate, shall be reported to the Sponsor as 
soon as possible, as well. 
 
See Section X, Subsection E of this protocol for additional information regarding 
adverse event classifications.  All medical events, regardless of classification, are 
required to be reported on the Adverse Event Report.  The completed Adverse Event 
Report must be submitted to the Sponsor in a timely manner.  The Investigator or 
Designee will also promptly provide the Sponsor with any additional requested 
information required for the Sponsor to comply with regulatory requirements.  If 
applicable per their reporting requirements, the Investigator or Designee will also 
report applicable adverse event(s) to their IRB. 
 
3. Revision 
Study subjects will be study completed for any revision, regardless of the component 
being revised.  In the event that removal of one or more of the implanted knee 
components is necessary, the Investigator will determine the best treatment and/or 
revision method for the subject. 
 
Prior to revision surgery, the Investigator or qualified Designee must document 
radiographic findings on the Physician Assessment of Postop Radiographs.   
 
Once the revision surgery has been completed, the Investigator or qualified Designee 
must complete an Adverse Event Report as well as a Study Completion form 
terminating the subject from the study.  For the study completion status, select “Study 
Prosthesis Removed”.    
 
All explanted device information must be documented on an Explanted Device Form.  
In addition, all explanted devices must be returned to Zimmer Biomet using the 
Explant Procedure (Appendix F). 
 
4. Investigator Withdrawal 
The Investigator can choose to withdraw a subject from the study if the subject no 
longer meets study inclusion/exclusion criteria.  The reason for the Investigator’s 
withdrawal of the subject must be documented on the Study Completion form. 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 18 of 25 
 
5. Subject Withdrawal 
Study subjects may choose to withdraw from the study at any time, for any reason.  If 
possible, a final evaluation will be completed for any subject who no longer wishes to 
participate in the study.  The reason for the subject withdrawal must be documented 
on the Study Completion form. 
 
6. Lost to Follow-up 
A study subject will be considered lost to follow-up after they have missed a visit and 
attempts to locate and evaluate the subject using the procedure outlined below have 
failed.  All attempts to contact the subject are to be documented in the subject’s 
medical record and on the Study Completion form.  Missed visit(s) also must be 
documented using the Protocol Deviation form, unless the visit is retrospective. The 
first three contact attempts should be made by telephone, with additional attempts as 
outlined in the following table: 
 
If 
Then 
a response is not received after three 
(3) phone calls 
the Investigator or Designee should send a 
letter to the subject explaining the follow-
up agreement per the Informed Consent, 
and requesting a response from the 
subject. 
all attempts to contact the subject are 
unsuccessful or  the subject is 
contacted and chooses to withdraw 
from the study 
a Study Completion form will be 
completed and will specify the reason the 
subject is no longer participating in this 
study. 
 
7. Protocol Deviations 
Investigators should not deviate from the study protocol.  If a protocol deviation does 
occur, the deviation must be documented on the Protocol Deviation form and 
submitted to the Sponsor.  If applicable per their reporting requirements, the 
Investigator or Designee will also report applicable protocol deviations to their IRB. 
 
8. Study Termination 
Study subject participation is expected to end upon completion of the subject’s 2 year 
follow-up visit unless the subject voluntarily withdraws from the study, is withdrawn 
from the study by the Investigator, is lost to follow-up, undergoes revision to remove a 
study device, or expires.  Reason(s) for study completion must be documented on the 
Study Completion form. 
 
If the Sponsor decides to terminate the study early, the Sponsor will inform the 
Investigators of the reason for early study termination.  It is the responsibility of the 
Investigators to inform their IRB as applicable according to local and national 
laws/regulations. 
 
9. Modification of the Protocol 
All amendments to this clinical protocol shall be agreed to by the Sponsor and be 
recorded with a justification for the amendment prior to implementation.  Approval of 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 19 of 25 
 
the applicable IRB must be obtained prior to implementation, if required according to 
the local and/or national laws/regulations. 
E. 
Medical Events/Adverse Events Definitions and Classifications 
An adverse event is any unfavorable or unintended sign, symptom, or disease associated 
with the use of the study device, whether or not related to the device.  Adverse event is 
synonymous with complication or medical event.  All medical events, regardless of 
classification, are required to be reported on the Adverse Event Report case report form.  
The completed Adverse Event Report must be submitted to the Sponsor in a timely 
manner.  The Investigator or Designee will also promptly provide the Sponsor with any 
additional requested information required for Sponsor to comply with regulatory 
requirements.  If applicable per their reporting requirements, the Investigator or Designee 
will also report applicable adverse event(s) to their IRB.    
1. Classification of the Event 
Adverse Event (AE) [1]: 
An Adverse Event is defined as any untoward medical occurrence, unintended disease 
or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons, whether or not related to the investigational medical device. 
 
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. 
 
Serious Adverse Event (SAE) [1]: 
A Serious Adverse Event is any adverse event that 
a. led to death 
b. led to serious deterioration in the health of the subject, that either 
resulted in: 
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient or prolonged hospitalization, or 
4. medical or surgical  intervention  to  prevent  life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c. led to fetal distress, fetal 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. 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 20 of 25 
 
Adverse Device Effect (ADE) [1]: 
An Adverse Device Effect is an adverse event related to the use of a medical device. 
 
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 medical device. 
 
Note 2: This definition includes any event resulting from use error or from intentional 
misuse of the medical device. 
 
Serious Adverse Device Effect (SADE) [1]: 
A Serious Adverse Device Effect is an adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event. 
 
The Sponsor is responsible for determining the final classification of adverse events. 
 
If an Unanticipated Serious Adverse Device Effect (USADE) is identified it will be promptly 
reported to concerned Investigators and regulatory authorities as required by applicable 
regulatory requirements.  If applicable per their reporting requirements, the Investigator 
or Designee will report the USADE to their IRB. 
 
2. Intensity of Symptoms 
Mild: 
The subject is aware of the sign or symptom, but finds it easily tolerated.  The 
event is of little concern to the subject and/or little clinical significance.  The event 
is not expected to have any effect on the subject’s overall health or well-being. 
 
Moderate: 
The subject has discomfort enough to cause interference with or change in usual 
activities.   The event is of some concern to the subject’s health or well-being and 
may require medical intervention and/or close follow-up. 
 
Severe: 
The event interferes considerable with the subject’s usual activities.  The event is 
of definite concern to the subject and/or poses substantial risk to the subject’s 
health or well-being.  The event is likely to require medical intervention and/or 
close follow-up and may be incapacitating or life threatening.  Hospitalization and 
treatment may be required. 
 
NOTE:  The term “severe” refers to the intensity of the event and can be used with 
any event, without regard to whether or not it meets the criteria for being 
classified as “serious” or “unanticipated”.  For example, a subject can have a 
severe headache, but it is not a serious event. 
 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 21 of 25 
 
3. Relation to Device 
Not Related: 
There is no possible relationship between the adverse event and the implanted 
device. 
 
Uncertain: 
It is not known if there is a possible relationship between the adverse event and 
the device. 
 
Probably: 
There is a reasonable possibility that the adverse event was caused by the device. 
 
Definitely: 
There is no doubt the adverse event is directly related to the device. 
 
Medical Device Information Reporting 
For any adverse event with a relation to device of “Uncertain”, “Probably” or 
“Definitely”, a Medical Device Reporting Information Form (MDRIF, Appendix E) must 
be completed and submitted to the Study Manager within 7 days.  Other required 
supporting documentation that should be sent with the MDRIF:  
 
All subject x-rays  
 
Operative notes 
 
A summary detailing the subjects postoperative physical therapy regimen 
 
Subject activity level at the time the event occurred. 
 
4. Outcome Definitions 
The outcome is in relationship to the Adverse Event, not the treatment rendered for 
the event (if any). 
 
Resolved: 
The adverse event has been resolved and/or no further treatment is required to 
treat the reported condition or illness. 
 
Tolerated: 
The adverse event will most likely never be resolved.  The subject “tolerates” 
the illness or condition as a matter of life. 
 
Pending: 
Treatment or diagnostic studies were prescribed for the adverse event and the 
outcome of the adverse event is not yet known. 
 
Study Withdrawal: 
Due to the adverse event, the subject was withdrawn from the study. 
 
Device Revision/Removal: 
The adverse event resulted in the removal of a study device. 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 22 of 25 
 
 
Death: 
The outcome indicates the subject died as a direct result of the reported 
adverse event. 
 
Reoperation of Affected Joint: 
The adverse event resulted in reoperation of the study joint, but the 
reoperation did not include removal of a study device. 
 
5. Collection Approach 
The type of approach taken to collect adverse event information, whether systematic 
or non-systematic. 
 
Systematic: 
Based on checklists, questionnaires, or tests 
 
 
Non-Systematic: 
Based on spontaneous reporting and recording 
F. 
Monitoring of the Study 
Prior to initiating the clinical study, the Sponsor will conduct a site initiation visit to ensure 
the Investigator(s) and study staff understands the study protocol and requirements and 
have adequate time and resources to implement and conduct the study.  Prior to study 
initiation, the Investigator must have a fully executed CTA and IRB approval of the study 
protocol and the study Informed Consent. 
 
During the course of the study, the Sponsor will conduct periodic central monitoring and 
maintain contact with the study staff to monitor compliance and evidence of adverse 
events, in accordance with the Sponsor’s policies and procedures.  The Sponsor will 
address any identified non-compliance with the executed CTA, study protocol, and 
applicable regulatory requirements. 
 
If onsite monitoring visit(s) are deemed appropriate by the Sponsor, the Investigator will 
permit representatives of the Sponsor’s monitoring team to have direct access to inspect 
all source data/documents, study documents/binders, corresponding sections of study 
subject medical/hospital records, and any other documents relevant to the study.  All 
Sponsor visits (including site initiation) will be documented using the Monitoring Visit Log 
(Appendix C). 
 
 
Risk Analysis 
XI.
This post-market clinical study is classified as minimal risk [2] and there are no anticipated risks 
specific to study participation other than the potential loss of confidentiality.  There are no 
experimental procedures in this study, and participation in this study is not anticipated to affect 
the medical treatment of enrolled subjects. 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 23 of 25 
 
The NexGen knee components being studied are post-market, non-investigational devices 
cleared by the FDA via 510(k).  The subjects included in this study could receive the devices 
without participating in the study. 
 
NexGen TM Monoblock Tibia (K012866, K020295, and K031462) 
 
NexGen TM Modular Tibia (K072160) 
 
When used in accordance with product labeling, the risks associated with the use of NexGen 
cementless knee components are similar to those of standard, metal-on-polyethylene 
cementless knee systems used for the same clinical indication or purpose.  These risks are 
categorized below as either general surgical risks or risks associated with a cementless total knee 
arthroplasty procedure/study device. Unanticipated adverse events can also occur. 
A. General Surgical Risks 
General surgical risks and post-operative adverse events can occur with any surgery and 
include, but are not limited to: 
 
Anesthetic complications/reactions 
 
Bleeding and/or excessive blood-loss 
 
Transfusion reaction 
 
Chronic Pain 
 
Post-operative infection 
 
Vascular injury 
 
Delayed wound healing 
 
Deep vein thrombosis (DVT) 
 
Nerve injury 
 
Death 
B. Risks Associated with Cementless Total Knee Arthroplasty/Study Device 
Potential adverse events associated with cementless total knee arthroplasty include, but 
are not limited to: 
 
Loosening or fracture/damage of the prosthetic knee components or surrounding 
tissues. 
 
Dislocation and/or joint instability. 
 
Malalignment of the prosthetic knee components. 
 
Bone fracture or nerve damage. 
 
Swelling or infection. 
 
Leg length discrepancies. 
 
Poor range of motion. 
 
Pain. 
 
Venous thromboembolic disease. 
 
Inflammation. 
 
Metal sensitivity. 
 
Corrosion of metal components (the significance and long-term implications are 
uncertain and await further clinical evidence and evaluation). 
 
Wear debris can initiate osteolysis which may result in loosening of the implant. 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 24 of 25 
 
Minimization of Risk 
Complications and/or failure of prosthetic implants are more likely to occur in patients with 
unrealistic functional expectations, heavy patients, physically active patients, and/or with 
patients who fail to follow through with the required rehabilitation program.  Physical activity or 
trauma can result in loosening, wear, and/or fracture of the implant.  The patient must be 
counseled about the capabilities of the implant and the impact it will have on his or her lifestyle.  
The patient must be instructed about all postoperative restrictions, particularly those related to 
occupational and sports activities and about the possibility that the implant or its components 
may wear out, fail or need to be replaced.  The implant may not last the rest of the patient’s life, 
or any particular length of time. Because prosthetic implants are not as strong, reliable, or 
durable as natural, healthy tissues/bones, all such devices may need to be replaced at some 
point. 
 
 
Statistical Considerations 
XII.
Performance of the commercially available NexGen TM Monoblock Tibia and NexGen TM 
Modular Tibia used in primary cementless tibia total knee arthroplasty will be evaluated 
for radiographic parameters, pain and function, and survival of the device.  Data collected 
in this study will be summarized descriptively and descriptive summaries will be the basis 
of any study reports issued.  These summaries may be used for interim study reports and 
may also be used to support regulatory submissions, presentations, and/or publications.  
Additional surgical technique and instrumentation data may be collected and evaluated. 
A. General Statistical Methods 
Statistical methodology will consist of summarizing collected data descriptively.  
Categorical data (e.g., gender or race) will be summarized using counts and percentages, 
and 95% Confidence Interval (CI), over the time periods of interest.  Continuous data, such 
as age, will be summarized by using means, medians, standard deviation, minimum, 
maximum, and 95% CI over the time periods of interest.  Implant survival and return to 
function will be summarized using a Kaplan-Meier method and presented with rates (as 
percentages) and confidence intervals.   
B. Sample Size 
A minimum of 132 subjects are to be enrolled in this study, with approximate equal 
distribution of at least 66 NexGen TM Monoblock and 66 NexGen TM Modular subjects.  
The NexGen TM Monoblock Tibia and NexGen TM Modular Tibia are considered 2 single-
arms being analyzed separately.   Sample size is based upon 6 to 10 sites enrolling between 
22 to 30 subjects per site.   
 
Based on NexGen’s expected success rate of 98% at two years on the primary endpoint and 
using a 10% non-inferiority margin against a 98% performance goal, 57 subjects are required 
to achieve 80% power to test non-inferiority.  57 subjects also allow the Sponsor to control 
the Type-1 alpha error at 0.05.  Assuming a 12% loss to follow-up over 2 years, 
approximately 66 subjects need to be enrolled for each single arm. 
 
 

 
NexGen TM Tibia Clinical Study: CONFIDENTIAL 
Protocol # K.CR.I.G.16.34 
July 17, 2017 – Version 1.0 
 
Page 25 of 25 
 
 References 
XIII.
 
[1] ISO 14155:2011(E). Clinical investigation of medical devices for human subjects – Good 
clinical practice. 
 
[2] US Food and Drug Administration. eCFR – Electronic Code of Federal Regulations Title 21. 
Retrieved April 25, 2017, from https://www.ecfr.gov/cgi-bin/text-
idx?SID=e0cb187b56d9cb0279bb080f88b8121d&mc=true&tpl=/ecfrbrowse/Title21/21tab_02.t
pl. 
 
[3] Fricka KB, Sritulanondha S, McAsey CJ. To Cement or Not? Two-Year Results of a Prospective, 
Randomized Study Comparing Cemented Vs. Cementless Total Knee Arthroplasty (TKA). J 
Arthroplasty. 2015 Sept;30(9 Suppl):55-58.