A Multi-center Outcomes Clinical Study of the PyroTITAN™ HRA Shoulder Implant in Humeral Head Resurfacing
Conditions: Arthritis
Sponsor: Smith & Nephew, Inc.

Confidential 
 
Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2        
 
 
 
 
 
 
 
 
A Multi-center Outcomes Clinical Study of the PyroTITAN™ HRA 
Shoulder Implant in Humeral Head Resurfacing 
 
 
 
Study ID Number: CP-HRA-002 
Protocol Date: 27-May-2013 
Amendment 1 
Revision 2 
 
 
 
Ascension Orthopedics, Inc. 
A 
8700 Cameron Rd, Suite 100 
Austin, Texas, 78754 
U.S.A. 
 
Legal Representative: 
Integra LifeSciences Services (France)  
Immeuble Séquoia 2, 97 allée Alexandre Borodine 
Parc technologique de la Porte des Alpes 
69800 Saint Priest, France 
 
 
This document contains confidential information belonging to Ascension Orthopedics Inc. Except as 
may be otherwise agreed to in writing, by accepting or reviewing these materials, you agree to hold 
such information in confidence and not to disclose it to others (except where required by applicable 
law), nor to use it for unauthorized purposes. In the event of actual or suspected breach of this 
obligation, Ascension Orthopedics, Inc. should be promptly notified. 
 

Confidential 
 
Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2        
 
APPROVAL OF PROTOCOL 
 
 
 
VERSION 
DATE 
REASON FOR UPDATE 
Amendment 1 
27-May-
2013 
Change of 3, 4 and 8 year timepoints to site visit 
Inclusion criteria change from 18 to 21 years  
 
 
Title 
A Multi-center Outcomes Clinical Study of the 
PyroTITAN™ HRA Shoulder Implant in Humeral Head 
Resurfacing 
 
EudraCT 
Not Applicable 
Protocol N° 
CP-HRA-002 
Version 
Revision 2 
Date 
27-May-2013 
 
 
Sponsor 
             
Stan Harris 
Senior Director of Clinical 
Affairs                                       
                                                  
 
 
        Date: 
 
       Signature: 
Principal Investigator  
                                                         Date:  
                                                        Signature:  
 
 
 
 

Confidential 
 
Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2        
 
CLINICAL INVESTIGATION PLAN SUMMARY 
 
TITLE 
A Multi Center Outcomes Clinical Study of the PyroTITAN™ HRA 
Shoulder Implant (Ascension Orthopedics, Austin TX) in Humeral Head 
Resurfacing 
SPONSOR 
Ascension Orthopedics, Inc 
 
OBJECTIVES 
The primary objective is to determine success of the PyroTITAN ™ HRA 
Shoulder Prosthesis as defined by no revisions, no device related 
complications requiring surgical replacement and freedom from chronic 
dislocation. 
The secondary objectives of this investigation are to evaluate the 
functionality, and radiographic performance of the PyroTITANTM HRA 
Shoulder prosthesis. 
INDICATION  
Subjects with shoulder replacement conditions associated without rotator 
cuff deficiencies, fractures or tumors. 
CLINICAL 
INVESTIGATION  
DESIGN 
This post market clinical investigation plan is for a multi-centre 
prospective, non-randomized, non-comparative, open investigation. 
NUMBER OF  
SUBJECTS 
It is anticipated that a total of 387 subjects may be enrolled. It is 
anticipated that a minimum of 20 subjects will be recruited at each 
investigational site. 
TARGET 
POPULATION 
Subjects who have presented at an investigation centre with a shoulder 
pathology justifying shoulder resurfacing that are not showing signs of 
associated rotator cuff deficient conditions and who have a functioning 
glenoid. 
LENGTH OF 
CLINICAL 
INVESTIGATION  
Subjects included in the clinical investigation will return for follow-up 
visits at first post op visit 3 month (1 – 120 days), 6 months and 1, 2, 3, 
4, 5, 8 and 10 years post-treatment. The recruitment period is estimated 
as 48 months with anticipated investigation duration of 168 months. 
PERFORMANCE 
Primary endpoint: absence of device related complications resulting in 
revision or removal of components. 
Secondary endpoints: To demonstrate postoperative functionality and 
radiographic performance at 2, 3, 4, 5, 8 and 10 years post treatment, as 
compared with pre-treatment results through:  
 ASES Score improvement  
 Patient satisfaction 
 WOOS 
 Constant Score 
 EQ-5D Quality of Life Questionnaire 
 Radiographic success  (X-Ray and MRI) 
SAFETY 
Adverse events will be recorded and reported appropriately throughout 
the investigation to assess safety. 

 
 
Confidential                                                                     Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2 
 
 
 
 Table of Contents 
 
2.0 Subject Management Table ............................................................................ 1 
3.0   Introduction ................................................................................................... 1 
4.0  
Purpose of Investigation .............................................................................. 1 
5.0 
Study Design ............................................................................................... 2 
5.1 
General .................................................................................................... 2 
5.2 
Definition of Terms ................................................................................... 3 
5.3 
Subject Eligibility Criteria ......................................................................... 4 
5.4 Screening / Enrollment ................................................................................ 6 
5.5  Success/ Failure Criteria ............................................................................ 7 
6.0  
Study Procedures........................................................................................ 8 
6.1 Pre-Operative Management ........................................................................ 8 
6.2 
Operative Management ........................................................................... 9 
6.3 
Post- Operative Management .................................................................. 9 
6.4 
Radiograph Requirements:  X-Ray and MRI .......................................... 15 
6.5 Subject Withdrawals .................................................................................. 22 
7.0 
Revision/Re-operation ............................................................................... 22 
8.0 
Lost To Follow-Up ..................................................................................... 23 
9.0 
Adverse Events ......................................................................................... 23 
9.2 
Serious Adverse Events (SAEs): ........................................................... 24 
9.3 
Unanticipated Serious Adverse Device Effect (USADEs): ..................... 24 
9.4 
Anticipated Adverse Events: .................................................................. 24 
9.5 
Adverse Event Severity Determination: ................................................. 25 
9.6 
Adverse Event Reporting: ...................................................................... 26 
10.0     Termination of Subject Participation ....................................................... 27 
11.0 Statistical Methods .................................................................................... 27 
11.1 
Purpose .............................................................................................. 27 
11.2 
Study Design ...................................................................................... 28 
11.3 
Sample Size and Power Analysis ....................................................... 28 
11.4 
Treatment Assignment ....................................................................... 29 
11.5 
Interim Analysis .................................................................................. 29 

 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
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11.6 
Data Analysis ...................................................................................... 29 
11.7 
Primary Endpoint ................................................................................ 29 
11.8 
Secondary Endpoint ........................................................................... 29 
11.9 
Other Endpoints .................................................................................. 30 
12.0  Risk Analysis ............................................................................................ 30 
13.0 Device Descriptions .................................................................................. 32 
14.0 Investigator Responsibility ........................................................................ 33 
14.1   Investigator Regulatory Binder .............................................................. 34 
14.2 
Case Report Form Completion ........................................................... 34 
15.0    Institutional Review Board (ETHICS BOARD) Action .............................. 35 
16.0   Informed Consent ..................................................................................... 35 
17.0 Review of Source Documents ................................................................... 37 
18.0  Record of Device Inventory ...................................................................... 37 
19.0 Sponsor Obligations .................................................................................. 38 
19.1   Investigator Training .............................................................................. 38 
19.2   Monitoring .............................................................................................. 38 
19.3   Sponsor Study Termination ................................................................... 38 
20.0   Changes to Investigational Plan ................................................................ 39 
21.0   Confidentiality ........................................................................................... 39 
22.0   Withdrawal or Termination of the Clinical Investigation ............................. 40 
 
 
Appendix A - Case Report Forms 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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CP-HRA-002 
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2.0 Subject Management Table 
 
 
 
* If available    ** If applicable 
VISIT INTERVAL  
Pre-Op 
<=180 days 
Prior to Surgery 
Day 
Day of 
surgery 
1st Post-Op 
(1–120 days) 
 3 Mo 
Follow Up 
Post-Op  
6 mo 
Follow Up 
Post-Op  
12 mo 
Follow Up 
Post-Op  
24 mo 
Follow Up 
Post-Op  
36 mo 
Follow Up 
Post-Op  
48 mo 
Follow Up 
Post-Op  
60 mo 
Follow Up 
Post-Op  
96 mo 
 Follow Up 
Post-Op  
120 mo 
Follow Up 
VISIT 
Visit 1   
Visit 2   
Visit 3  
Visit 4  
Visit 5  
Visit 6   
 
Visit 7 
 
Visit 8 
Visit 9 
 
Visit 10 
 
Visit 11   
 
Screening 
Surgery 
Post Op 
Post Op 
Post Op 
Post Op 
Post Op 
Post Op 
Post Op 
Post Op 
Post Op 
X-Ray Evaluation 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MRI Evaluation* 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion 
Criteria Worksheet 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Constant Score  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
WOOS Score 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D  Evaluation 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ASES Score  Evaluation 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Visual Analog Scare for 
Satisfaction 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Visual Analog Scale for 
Pain 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Operative Detail 
 
X 
 
 
 
 
 
 
 
 
 
Adverse Event** 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Withdrawal 
Forms(as needed)** 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
 
Confidential                                                                     Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
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Revision 2 
 
3.0   Introduction 
 
  With the increase of activity in younger patients, glenohumeral arthritis has also 
increased.  These patients seek relief from pain but also require the ability to return to full 
or near participation in those recreational sports activities. (Miller2008).  Total shoulder 
arthroplasty, associated with reports of high rates of early glenoid wear, aseptic loosening, 
and the reduced return of full function is an effective solution for less active patients. 
Persistent pain related to glenoid arthrosis after hemiarthroplasty or humeral head 
resurfacing with metal components is often a barrier for many patients. Economic 
pressures require the implant system allow an efficient continuum of staged intervention 
while meeting increasing demands. The design must replicate anatomy; allow a range of 
treatment options including bone conservation, minimization of implant on bone wear, 
avoidance of a cemented polyethylene glenoid component when the glenoid is intact, and 
the staged addition of a glenoid implant or conversion to a full shoulder or to a reverse 
shoulder implant in those patients whose disease process continues to advance.  
Hemiarthroplasty and humeral head resurfacing (HRA) is indicated in those patients with an 
intact rotator cuff, a congruent glenoid, and no history of instability or subluxation where an 
alteration in humeral version is required or where a change in version, neck shaft angle or 
head height would be required after a nonunion or mal union of a fracture.  HRA allows 
earlier intervention, restoration of function, higher patient satisfaction and the ability to 
stage the intervention to meet the patient needs.  
 
 
4.0  Purpose of Investigation 
 
The purpose of the study is to determine the difference between pre- and post-operative 
levels of patient satisfaction, shoulder function, radiographic alignment, and shoulder 
pain in patients receiving a PyroTITANTM HRA Shoulder prosthesis for glenohumeral 
arthritis.  The clinical performance of the PyroTITANTM HRA Shoulder prosthesis 

 
 
 
 
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Protocol Date: May 27, 2013               
 
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implanted as a shoulder resurfacing prostheses (i.e. humeral only) evaluated with 
respect to: 
 
 Short and long term clinical response (ASES, WOOS, Constant Score and 
EQ-5D, VAS Pain Score) 
 Complication rates (including intraoperative) 
 Peri-operative clinical parameters (e.g. skin to skin, operative approach) 
 Radiographic outcome 
 Patient Satisfaction (VAS Questionnaire) 
 
 
5.0 Study Design 
 
5.1 General 
 
This study is designed as a multi-center, nonrandomized, uncontrolled, unblinded, 
prospective clinical outcomes investigation to evaluate the short, mid and long term 
performance of the PyroTITANTM HRA Shoulder prosthesis humeral replacement.  The 
PyroTITANTM HRA Shoulder prosthesis device configuration will include humeral 
resurfacing CAP without cement.  Patients will be selected for recruitment into the study 
based upon the normally accepted criteria for primary shoulder resurfacing arthroplasty.   
 
The investigation will be conducted by up to 10 International surgeons experienced in HRA.  
387 subjects with PyroTITANTM HRA Shoulder prosthesis arthroplasties will be implanted 
and followed for 10 years.  It is anticipated that initial patient accrual will be carried out over 
a twelve-month period. Amendment 1 of this study increased the number of subjects, 
expanding the enrollment time to 48 months.  Patient selection procedures, data to be 
collected and patient follow-up schedules are detailed in the following sections of this 
protocol.  In the event that the implanted device is removed, the event will be noted on the 
Adverse Event case report form. Device-related adverse events include, but are not limited 
to: breakage, infection, loss of fixation, dislocation and wear. 
 

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2 
 
5.2 Definition of Terms 
 
ASTM = American Society for Testing Materials.  Organization established to develop 
standardized test methods and material specifications. 
Clinical Investigation = Human research study administered under a detailed study 
protocol. 
Clinical Investigator = Person responsible for administering the clinical investigational plan 
and reporting the study data for the respective investigational site.  If there are to be 
multiple clinical investigators, then a primary investigator is designated and those remaining 
are co-investigators. 
CRF = Case Report Form.  Form used for recording the Subject data required by the 
clinical protocol. 
CRO = Contract Research Organization.  A firm employed by the Sponsor to oversee 
various aspects of the clinical investigation. 
FDA = U.S. Food and Drug Administration  
Clinical Investigational Plan (CIP) = Written document describing how the clinical 
investigation will be conducted. 
Investigator’s Regulatory Binder = a binder provided to the investigator by the Sponsor and 
maintained by the investigational site.  The binder includes regulatory documents, Ethics 
Committee documents, correspondences, investigator’s responsibilities, study protocol 
correspondence, all applicable federal regulations, investigator’s CV and agreement, and 
other contents deemed applicable by the Sponsor.  
Investigational Site = Institution where the clinical investigation will be administered. 
IPC = Informed Patient Consent. 
ETHICS BOARD/COMMITTEE = Institutional Review Board.  A group of people formally 
designated by an institution to review and approve all biomedical research involving 
humans, which is conducted at the hospital/clinic to assure that the rights, welfare and 
safety of subjects, are protected. 
IRR = Independent Radiographic Reviewer 

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
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Monitor = Person(s) designated by the Sponsor to review medical records and other source 
documents pertaining to an investigational study. 
Research Subject = Subject who gave his/her consent to participate in the clinical 
investigation. 
Sponsor = Person/Organization responsible for overseeing the conduct of the clinical 
investigation. In this case, Ascension Orthopaedics, Inc. 
Source Documentation = Original documents, data, and records (e.g., hospital records, 
clinical and office charts, patient completed questionnaires, study worksheets, laboratory 
notes, X-ray films, other Subject information, etc.) that document Subject care and 
associated procedures in a clinical investigation. 
TSR= Total Shoulder Resurfacing 
TSA = Total Shoulder Arthroplasty 
TJR = Total Joint Replacement 
UADE = Unanticipated Adverse Device Effect is any serious adverse effect on the health or 
safety or any life-threatening problem or death caused by, or associated with a device, if 
that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence. 
VAS = Visual Analog Scale 
 
5.3 Subject Eligibility Criteria 
 
This section details the entry criteria for Subject eligibility for participation in this clinical 
investigation.  Demographic, clinical, and radiographic requirements that must be met (in 
addition to the diagnostic criteria) are described below. Subjects will be selected for 
recruitment into this study from the general diagnosis population defined for primary Total 
Shoulder Resurfacing as an end-stage condition of the Shoulder joint that is refractory to 
non-surgical treatment (see  Inclusion Criteria and  Exclusion Criteria).   
 
Subjects who do not meet all of the inclusion criteria or meet any exclusion criteria are 
automatically excluded from study consideration and participation. Subjects who meet all 
entry criteria and are properly consented, may be excluded from participation because of: 

 
 
 
 
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Protocol Date: May 27, 2013               
 
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 surgical preference,  
 withdrawal of consent for study participation,  
 other reasons. 
 
 
Inclusion criteria 
 
1. Patients selected for inclusion will present for primary shoulder surface replacement 
or arthroplasty with any of the following diagnoses:  
 
a. Osteoarthritis 
b. Rheumatoid / Inflammatory Arthritis 
c. Post-traumatic arthritis.   
d. Focal and large (Hill-Sachs) osteochondral defects. 
2. Subject is able to or capable of providing consent to participate in the clinical 
investigation. 
 
3. Subject agrees to comply with this protocol, including participating in required follow-
up visits at the investigations site and completing study questionnaires. 
 
4. Subject is at least 21 years of age and skeletally mature at the time of surgery. 
 
Exclusion Criteria 
Patients will be excluded from participation if they: 
1. Have destruction of the proximal humerus to preclude rigid fixation of the 
humeral component 
2. Insufficient bone quality as determined by intra-operative evaluation 
3. Have arthritis with defective rotator cuff 
4. Have had a failed rotator cuff surgery 
5. Have loss of musculature, neuromuscular compromise or vascular 
deficiency in the affected limb rendering the procedure unjustified 
6. Have evidence of active infection  

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
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Revision 2 
7. Present with a condition of neuromuscular compromise of the shoulder 
(e.g., neuropathic joints or brachioplexis injury with a flail shoulder joint) 
8. Are unwilling or unable to comply with a rehabilitation program or would fail 
to return for the postoperative follow-up visits prescribed by the protocol 
9. Are skeletally immature. 
10. Have a known allergic reaction to pyrocarbon 
11. Have other conditions such as central nervous system disturbances, alcohol 
or drug addiction, etc. that may make effective evaluation of the joint 
replacement difficult or impossible  
12. Are currently participating in another clinical study 
13. Have known, active metastatic or neoplastic disease 
14. Are taking > 10mg/day corticosteroids (e.g. prednisone) excluding inhalers, 
within 3 months prior to surgery 
15. Are under 21 years of age or over 75 
16. Require glenoid replacement (Glenoid Classification) 
 
Obesity, heavy labor, metabolic disorders, disabilities of other joints and active sports 
participation are relative indications for study exclusion since these conditions tend to place 
the patient at higher risk of failure than other arthroplasty patients. Consideration of such 
patients for study inclusion is at the discretion of the investigator. 
 
5.4 Screening / Enrollment 
 
The surgeon will recommend whether the patient should be implanted with this device even 
if the patient decides not to take part in the study. 
The patient must be screened against the inclusion and exclusion criteria (Section 5.3). 
Where a subject fails to fulfill any element of the inclusion and exclusion criteria, this will be 
documented. The subject will not be advanced any further into this investigation. Screened 
Subjects who meet all eligibility criteria and consent to participation must be entered into 
the study.     
 

 
 
 
 
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Protocol Date: May 27, 2013               
 
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The subject will only be allocated to the next available investigational subject number when 
it is confirmed that the subject is eligible and the procedure will ensue. This number will 
consist of the center study number followed by 001 for the first patient, 002 for the second 
patient and so on, (e.g. 2001 site 2 subject 1). This number will then become the unique 
identifier of the subject and will be written on each page of the CRF and all other study 
documentation relating to that subject.  A master subject list which will be kept strictly 
confidential and will not be removed from the Investigational Site will record the full name, 
subject number and clinic record number for each enrolled subject. 
 
Any subject who wishes to withdraw from this investigation on his/her own accord and for 
whatever reason is entitled to do so without obligation and prejudice to further treatment. In 
addition, the Investigator may decide for reasons of medical prudence, to withdraw a 
subject. In either event, the Investigator will clearly document the date and reason(s) for the 
subject’s withdrawal from this investigation in the clinic notes and should indicate whether 
or not he considers it related to the device. 
 
5.5  Success/ Failure Criteria 
Clinical requirements for success at 24, 60 and 120 months: 
 Device remains implanted 
 Absence of device-related complications requiring surgical replacement, removal, or 
augmentation of components 
 Freedom from chronic dislocation 
 
Radiographic and MRI requirements for success: 
 No evidence of device radiolucency > 2mm 
 
Anatomic alignment 
 
 
 

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
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Revision 2 
6.0  Study Procedures 
 
 
6.1 Pre-Operative Management 
 
Pre-admission testing may be conducted to satisfy the medical/surgical requirements of 
each Investigator, hospital or institution participating in the study. Such testing is not 
intended to determine comparability of the study device and will, therefore, not be 
documented by the Sponsor. The investigators will obtain the clinical information and 
record it in the medical chart.  Data collected will address the following:  demographic 
information, age, sex, date of birth, patient reported height and weight, hand dominance, 
side of injury, history of present illness,  diagnosis, mechanism of injury, smoking and 
diabetes status, history of fracture and x-ray availability (all of which are standard data 
collected during routine history taking).  Patients will be asked to verify the information 
collected from the medical chart and update information as appropriate at designated post- 
operative visits.  Prior to surgery, the following procedures must be completed for each 
enrolled subject to satisfy study requirements: 
1. Executed Informed Patient Consent  
2. Verification of all inclusion and exclusion criteria 
3. Subject medical history review 
4. Radiographic (X-ray and MRI) evaluation 
5. Clinical evaluation 
6. Subject self-assessments 
As part of the pre-operative assessment of each study subject, the investigator will 
complete the Constant Score CRF based on source documentation.  The Subjects will 
obtain radiographs, complete the WOOS, EQ-5D, the VAS Scales, ASES Shoulder 
Evaluation, and update Health History Profile.  The center will submit x-rays and MRI’s for 
independent evaluation.  All data will be compared with the follow-up data obtained at each 
study interval.    
   
 
 

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
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Revision 2 
 
6.2 Operative Management 
 
Each investigator will complete an Operative Details CRF based on source documentation 
that provides specific information from the Subject’s surgery, such as surgical technique, 
catalog and lot numbers for implanted device.  Any complications that occurred during the 
surgery are reported using the Operative Complications CRF.  
 
The anesthesia procedure will follow the normal clinical practice at the investigation site.  
All sites are to use general, spinal or epidural anesthesia.  Further, it is strongly 
encouraged that the anesthesia be standardized across all study Subjects within one 
institution.   
 
In addition, each individual site will designate the surgical approach and any ancillary 
procedures on the Operative case report form.  A surgical technique for the PyroTITANTM 
HRA Shoulder prosthesis will be provided to each investigator participating in the study. 
 
The Investigator should record all of the following information after the surgery:   
 Subject Historical Profile 
 Operative Detail 
 Pre-op WOOS Score 
 Pre-op ASES Score 
 Pre-op Constant Score 
 Pre-op Visual Analog Scale (Pain) 
 Pre-Op X-rays, MRI and/or CT films 
 
6.3 Post- Operative Management 
 
Immediate post-operative management is at the discretion of the surgeon and support staff.  
Rehabilitation programs are somewhat individualized and variables such as age, health 
and physical fitness of the subject must be considered by the surgeon when recommending 

 
 
 
 
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Protocol Date: May 27, 2013               
 
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a rehabilitation program.  The subject should be encouraged to report any unusual changes 
in the operated extremity to the physician. If any such change is found to be related to the 
device or procedure, such a report would necessitate submission of an Adverse Event CRF 
to the Sponsor. General, accepted practices for post-operative care should be followed for 
each Subject. 
 
Follow up intervals will be calculated from date of surgery as follows: 
 Pre-Operative   
- 180 to -1 day 
 3 months          
1 - 120 days 
 6 months         
 180 days +/- 30days 
 12 months 
365 days  +/- 60days 
 24 months 
730 days +/- 60days 
 36 months  
1095 days +/- 90 days         
 48 months 
1460 days +/- 90 days 
  
 60 months 
1825 days  +/- 90 days 
 96 months 
2920 days +/- 90 days  
 
 120 months 
3650 days +/- 90 days 
 
The following case report forms that will be completed and submitted to the sponsor in the 
noted intervals can be found on the Time and Event Table Section 2.0. 
 
Clinical Outcome Forms 
 
All clinical outcome forms will be performed on each study subject at the intervals specified 
in Section 2, and will be performed per the standard of care at the institution.  The research 
associates/coordinators, or medically qualified designee (not the Surgeon) per their 
standard of care for patient management purposes, will perform all of the assessments.  
The following will be assessed: ASES Shoulder Score, Constant Score, WOOS Score, EQ-
5D Health Questionnaire, VAS Pain and Satisfaction Scale, and strength and range of 
motion. 
 

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2 
 
ASES Shoulder Score 
 
The ASES Shoulder Score is a functional outcome tool that has been validated for various 
shoulder conditions (Leggin et al., 1999).  This form is commonly used during the clinical 
process.  The ASES Shoulder Score form consists of questions pertaining to patients’ 
satisfaction, function and pain as related to the shoulder.  The subject will take between 10 
to 15 minutes to complete the test.  If the subject requests assistance or a phone 
consultation is done, completion of the form will be completed with minimum or no 
assistance from the coordinator.  The coordinator can clarify a question but will not influence 
the subject.   
The subject will provide the best possible answer for that day.  The form will be completed 
preoperatively and postoperatively (3 months, 6 months, 12 months, 24 months, 36 months, 
48 months, 60 months, 96 months and 120 months).   
 
WOOS Score 
 
The WOOS Score is a quality of life questionnaire that has been validated for various 
shoulder conditions.  This form is used during the clinical process.  The WOOS Score form 
consists of 4 components, Physical Symptoms, Sports/Recreation/Work, Lifestyle, and 
Emotions pertaining to the patients’ satisfaction, function and pain as related to the 
shoulder.  The subject will take between 10 to 15 minutes to complete the form.  The form 
will be completed with each mailing and returned to the Investigator. If the subject requests 
assistance or a phone consultation is done, completion of the form will be completed with 
minimum or no assistance from the coordinator.  The coordinator can clarify a question but 
will not influence the subject.   
The subject will provide the best possible answer for that day.  The form will be completed 
preoperatively and postoperatively (3 months, 6 months, 12 months, 24 months, 36 
months, 48 months, 60 months, 96 months and 120 months).   
 
 

 
 
 
 
Confidential                                                                      Ascension Orthopedics 
Protocol Date: May 27, 2013               
 
CP-HRA-002 
Amendment 1 
Revision 2 
Visual Analog Scale (VAS) 
 
The Visual Analog Scale (VAS) form assesses pain, shoulder pain and satisfaction as it 
relates to the effected shoulder.  The subject completed form requests the subject marks 
the response on a line scale with a single slash.  The form will be completed at each 
testing session. Completion of the form will be completed with minimum or no assistance 
from the coordinator.  The coordinator can clarify a question but will not influence the 
subject.   
 
The subject will provide the best possible answer for that day.  The subject will provide the 
best possible answer for that day.  The form will be completed preoperatively and 
postoperatively (3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 
months, 96 months and 120 months). 
 
EQ-5D Quality of Life Questionnaire 
 
The EQ-5D Questionnaire consists of information pertaining to the current health status of 
the patient at the time of evaluation. The EQ-5D questionnaire measures physical, 
emotional, and social status. The subject will take between 10 to 15 minutes to complete 
the test.  The form will be completed at each testing session. The subject will provide the 
best possible answer for that day.  The form will be completed preoperatively and 
postoperatively (3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 
months, 96 months and 120 months).The form will be completed with minimum or no 
assistance from the coordinator.  The coordinator can clarify a question but will not 
influence the subject.  The subject will provide the best possible answer for that day.     
 
Constant Score  
 
The Constant Score is a commonly used score of shoulder function.  
 Collection of this data will allow comparison with both US and European data. The 
Constant form consists of questions pertaining to shoulder pain, function, and strength.  The 

 
 
 
 
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form will be completed preoperatively and postoperatively (3 months, 6 months, 12 months, 
24 months, 36 months, 48 months, 60 months, 96 months,  and 120 months) after the 
patient has regained function. 
 
Strength 
Strength is given a maximum of 25 points in the Constant Score. The significance and 
technique of strength measurement has been, and continues to be, the subject of much 
discussion.  
The European Society for Shoulder and Elbow Surgery measures strength according to the 
following method: 
 
A spring balance is attached distal on the forearm.  
 
Strength is measured with the arm in 90 degrees of elevation in the plane of the 
scapula (30 degrees in front of the coronal plane) and elbow straight.  
 
Palm of the hand facing the floor (pronation).  
 
The patient is asked to maintain this resisted elevation for 5 seconds.  
 
It is repeated 5 times immediately after another.  
 
The average in pounds or kilograms (lb or kg) is noted.  
 
The measurement should be pain free. If pain is involved the patient gets 0 points.  
 
If patient is unable to achieve 90 degrees of elevation in the scapula plane the patient 
gets 0 points. 
 
 
 

 
 
 
 
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Range of Motion   
 
Flexion 
Flexion is when the arm is moving in a straightforward and upward motion. Normal range of 
motion for flexion of the shoulder joint is 170 to 180 degrees. The motion starts at 0 
degrees, or neutral, which is when the arms are at the side of the body with palms facing 
forward. 180 degrees is when the arms are straight overhead and elbows are by the ears. 
Anything beyond 180 degrees is considered hyperflexion. 
 
Extension 
Extension is when the arm is moving straight backwards. Normal range of motion for 
extension of the shoulder joint is 50 to 60 degrees. The motion starts at 0 degrees. Shoulder 
extension is the most powerful shoulder movement. 
 
External Rotation 
External rotation occurs when the lower arm rotates outward, away from the body while the 
elbow remains at the side. Normal range of motion for external rotation is 90 to 100 
degrees. For external rotation, 0 degrees is when the upper arm is at the side with the 
elbows bent 90 degrees. The lower arm is parallel to the floor, and the hand is pointing 
forward. 
 
Internal Rotation 
Internal rotation occurs when the lower arm moves inward, toward the body while the elbow 
remains at the side. Normal range of motion for internal rotation is 80 to 90 degrees. For 
internal rotation, 0 degrees is when the upper arm is at the side with the elbows bent 90 
degrees. The lower arm is parallel to the floor, and the hand is pointing forward. 
 
 
 
 

 
 
 
 
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Abduction 
Abduction is when the arm is moved outward from the side of the body. Normal range of 
motion for abduction of the shoulder joint is 170 to 180 degrees. The motion starts at 0 
degrees, which is when the arms are at the side of the body with palms facing forward. 180 
degrees is when the arms are straight overhead and elbows are by the ears. 
 
Adduction 
Adduction is moving the limb closer to or across the body. Normal range of motion for 
adduction is 45 degrees. The motion starts at 0 degrees or neutral, which is when the 
arms are at the side of the body with palms facing forward. 45 degrees is when the upper 
arm has moved across the front of the body toward the opposite side. 
 
The patient directed forms will be completed with minimum or no assistance from the 
coordinator.  The coordinator can clarify a question but will not influence the subject.  The 
subjects will provide the best possible answer for that day.  
 
 
As part of the post-operative assessment of each study Subject, the investigator will 
complete the Constant Score CRF based on source documentation.  The Subjects will 
obtain radiographs, complete the WOOS, EQ-5D, the VAS Scales, ASES Shoulder 
Evaluation, and update Health History Profile.  The center will submit x-rays and MRI’s for 
independent evaluation.  All data will be compared with the follow-up data obtained at each 
study interval.    
 
6.4 Radiograph Requirements:  X-Ray and MRI 
 
The shoulder radiographic views will consist of a true anterior-posterior in the scapular 
plane, internal and external rotation, axial lateral and an axillary lateral view.  The patient 
will be placed in a shoulder harness to maintain 30 degrees of scapular plane during the 
examination or subjects may be radiographed supine with wedge support.  Patients may 
come to the office with shoulder radiographs already completed at their first clinical visit.  

 
 
 
 
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Additional radiographs may be needed if the radiographs are of poor quality and/or do not 
provide adequate information on the humeral head.   
 
Radiographs will be completed at the following time periods: pre-operatively within 180 
days of surgery and post-operatively: 3 months, 6 months, 12 months, 2 years, 3 years, 4 
years, 5 years, 8 years and 10 years.  The following will be assessed on the radiographic 
evaluation: loosening of the humeral component, osseous structures, anatomic alignment, 
condition of the glenoid and joint congruity.      
 
The patient will not need radiographs if they have had a revision surgery and/or they are 
lost to follow-up.  Radiographs are obtained at the pre- and post-operative intervals, as 
designated on the Subject Management Schedule. 
 
 Radiographic evaluation parameters are provided below.  All radiographs are submitted to 
the Sponsor after the scheduled visit. To avoid potential bias, an independent radiographic 
reviewer (IRR) will evaluate all radiographs. The reviewer will complete the radiographic 
evaluation forms and forward them to the Sponsor for entry into the database. Data from 
the IRR radiographic evaluation will be used for determining the radiographic success 
criteria.   
 
General Instructions 
 All effort should be made to utilize the same X-ray machine with the same settings 
across time periods for each individual.  To ensure consistency in quality of the 
radiographs, it is recommended the kVp, mAs, FFD, and tube angles must remain the 
same for a given patient at all time periods.  
 Radiographs should be of adequate quality (not over or under exposed). 
 All radiographs should be performed using digital DICOM 3 uncompressed format. 
Digital files should be recorded onto the Study CD labeled with the required patient and 
visit identifiers. 
 All actions must be taken by the site to anonymize the radiographic images. 

 
 
 
 
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 Digital images must be submitted at 100% scale or true to size 
 For film, the film size should be appropriate to the size of the subject 
 Left or right lead markers must be utilized without superimposition of pertinent anatomy. 
 
 
AP SHOULDER RADIOGRAPH ACQUISITION  
External Rotation, Neutral Rotation, and Internal Rotation 
Scapular Plane 
 
View 
kVp 
mAs 
FFD 
Film Size 
Centering 
Patient Instruction 
AP 
External 
70-80 
 
10 
Between 
40 and 48 
inches 
(100-120 
cm) 
24 X 30 cm 
crosswise 
The central ray 
should be 
perpendicular to 
film centered to 
coracoid process 
The patient may be 
examined in the erect or 
supine position. The erect 
position is recommended 
whenever possible so 
that the patient’s body 
position can be adjusted 
to require little or no 
manipulation of the arm. 
Neutral 
Rotation 
70-80 
 
10 
Between 
40 and 48 
inches 
(100-120 
cm) 
24 X 30 cm 
crosswise 
The central ray 
should be 
perpendicular to 
film centered to 
coracoid process 
The patient may be 
examined in the erect or 
supine position. The erect 
position is recommended 
whenever possible so 
that the patient’s body 
position can be adjusted 
to require little or no 
manipulation of the arm. 
 
 
 
 
 
 
 
AP Internal 
70-80 
 
10 
Between 
40 and 48 
inches 
(100-120 
cm) 
24 X 30 cm 
crosswise 
 
The central ray 
should be 
perpendicular to 
film centered to 
coracoid process 
The patient may be 
examined in the erect or 
supine position. The erect 
position is recommended 
whenever possible so 
that the patient’s body 
position can be adjusted 
to require little or no 
manipulation of the arm. 
 
AP Shoulder 
 Place the patient in the erected position. 

 
 
 
 
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 Adjust the patient’s body to center the film to the coracoid process. Rotate the 
patient enough to place the blade of the scapula parallel with the plane of the film. 
 
External Rotation 
 Ask the patient to turn the palm of their hand forward. 
 Abduct the arm slightly and adjust it so that the coronal plane of the 
epicondyles is parallel with the plane to the film. 
Neutral Rotation 
 Ask the patient to rest the palm of the hand against his thigh. 
Internal Rotation 
 Ask the patient to flex their elbow, rotate the arm internally and rest the back of 
the hand on his hip.  
 Adjust the arm to place the coronal plane of the epicondyles perpendicular to 
the plane of the film. 
 If this positioning is too painful for internal rotation, the patient may turn away 
from the film. 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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AP External 
AP Neutral 
AP Internal Rotation 
 
 
                   
   
 
 
 
 
LATERAL SHOULDER RADIOGRAPH ACQUISITION 
 Axial Lateral and Axillary Lateral 
 
kVp 
mAs 
FFD 
Film Size 
Centering 
Patient Instruction 
 
 
Between 40 
and 48 inches 
(100-120 cm) 
18 X 24 
cm  
lengthwise 
Direct the 
central ray 
at angle of 
5 to 15 ° 
toward the 
elbow. 
Seat the patient at the 
end of the table with 
the shoulder centered 
to the midline of the 
table. The patient 
should be seated on a 
stool or chair high 
enough to enable him 
to extend the affected 
should over the 
cassette. 
 
Axial Projection 
 Place the cassette near the end of the table and parallel with its long axis. 
 Raise the patient’s arm on the affected side to a position as near as possible at right 
angles to the long axis of the body. 
 Have the patient lean laterally over the cassette until the shoulder joint is over the 
midpoint of the film and bring the elbow to rest on the table. 
 Flex the patient’s elbow 90° and place the hand in the neutral position. 

 
 
 
 
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 Have the patient bend his head toward the unaffected side. 
     
Axial Lateral 
Axillary Lateral 
I
 
Insert Image 
            
 
MRI Instructions 
 
1.5 TESLA or 3 TESLA MRI can be utilized for the evaluation.  The same MRI unit should 
be used for all evaluations, e.g, the original MRI is performed using a 1.5 Tesla unit all 
future evaluation for that patient should be performed on the 1.5 Tesla unit. 
 
Use same series for pre and post operative scans so imaging is comparable 
 
 AXIAL T1 : 
 
-Resolution 384 x 384 pixels  
 
 
-large field of view to include whole scapular body for  
 
 
            assessment of glenoid version 
 
 
-assess glenoid vault and muscle bulk of spinati 
 
 
 
AXIAL PD : 
 
-Resolution 512 x 512 pixels 
 
 
-small field of view to focus on glenohumeral joint region 
 
 
-good for PYC on post-op with less artefact 
 
 
-good assessment of interface between Pyrotitan and native  
 
           glenoid on post op 
 
 
 

 
 
 
 
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 
2ND AXIAL PD : 
Fat saturated 
 
 
-Resolution 384 x 384 pixels 
 
 
-small field 
 
 
-better for oedema,  cysts etc 
 
 
 
CORONAL PD  : 
- good for anatomic detail of cuff, labrum etc 
 
 
 
CORONAL T2  : 
STIR (this is by definition fat sat) 
 
 
- less artefact on post op so good for assessing cuff post op 
 
 
 
SAGITTAL T1 : 
Non fat sat 
 
 
-muscle atrophy 
 
 
-comparable to Goutallier type assessment of spinati for fatty  
 
          atrophy 
 
 
 
SAGITTAL T2 : 
Fat saturated 
 
 
-good detail and sensitive to fluid around / under prosthesis at  
 
            bone / prosthesis interface 
 
 
Radiograph / MRI Submission 
 
The preferred method of radiograph submission is by digital format. The digital images 
should be saved in JPEG-2000 or dicom format and submitted to the Sponsor on a CD and 
sent by FEDEX or other over-night carrier.  The date of film must either be on the x-ray and 
designated in the file name.  Subjects should be identified by their initials and Subject ID 
number.      
 
In the event digital images are not available, the site’s original radiographs for each x-ray 
view will be forwarded to the Sponsor. The Sponsor will make digital copies of the original 
radiographs and return the film copy to the investigational site. All radiographs will be de-
identified to the extent possible by the site prior to shipping to the sponsor. 
 
 

 
 
 
 
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6.5 Subject Withdrawals 
 
Pre-operative Withdrawal 
Subjects who withdraw from consideration prior to signing consent or who decline 
participation or who sign consent, but are pre-operatively excluded are considered “screen 
failures” and are not entered as subjects into the study.  No forms are required to be 
maintained at the Site or submitted to the Sponsor for screen failures. 
 
Intra-operative Withdrawal 
 
If a subject is withdrawn intra-operatively (e.g. inclusion/exclusion criteria, etc.), then a 
completed Operative Detail CRF must be submitted to the Sponsor in addition to those 
listed above.  
However, all data obtained up until the time of consent withdrawal will be available for 
analysis.  The Withdrawal CRF must be sent to the Sponsor. 
 
Post-Operative Withdrawal 
 
Subjects withdrawn from the study post-operatively (e.g., withdrawal of consent, etc.) who 
maintain the investigational components do not require continued follow-up in accordance 
with the study protocol.  However, all data obtained up until the time of consent withdrawal 
will be available for analysis.  The Withdrawal CRF must be sent to the Sponsor. 
 
7.0 
Revision/Re-operation 
 
Post-operative surgical procedures associated with the operative shoulder are categorized 
as Adverse Events.  If a Subject undergoes any surgical procedure on the operative 
shoulder in which all of the original Pyro-Titan Resurfacing Shoulder implant components 
are retained (debridement etc), the Subject is not withdrawn from the study and all follow-
up visits are maintained according to the Subject Management Schedule.  If the Pyro-Titan 
Resurfacing Shoulder prosthesis implant is removed then the Subject is considered 
revised, is withdrawn from the study, an Adverse Event and Study Completion CRFs must 

 
 
 
 
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be submitted to the Sponsor.  The remaining study-related follow-up visits are not required 
in the case of revision.  Every attempt should be made to retain the explanted device and 
return it to the Sponsor for evaluation. 
 
8.0 
Lost To Follow-Up 
 
There may be study subjects who will not or cannot return for follow-up examinations as  
prescribed in the protocol.  These individuals will be considered as non-compliant with the 
study protocol.  This group includes: 
 Subjects who refuse to return for follow-up, 
 Subjects who relocate without notifying the Sponsor or the Investigator, and cannot 
be located for continued follow-up arrangements. 
Subjects that are considered “lost to follow up” are not considered withdrawn from the 
study.  Sites should make every attempt to contact and schedule post-operative visits.  In 
the event a subject does not respond to telephone correspondences regarding a missed 
visit, a registered letter should be sent to the subject indicating the importance of the follow-
up visits and to contact the office immediately.  All correspondence to the subject must be 
documented within the subject’s source documentation. 
 
9.0 
Adverse Events 
 
For the purpose of this study, an adverse event is defined as any medical condition or 
event for which the subject seeks medical attention that, in the physician’s opinion has an 
association with the medical device or operative procedure. Adverse events may be mild, 
moderate or severe. All adverse events, device related or procedure related, are 
transcribed from source documentation onto an Adverse Event CRF and forwarded to the 
Sponsor (one Adverse Event per CRF). 
 
 
 

 
 
 
 
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9.1 Serious Adverse Events (SAEs): 
An adverse event that: 
 
Lead to death;  
 
Lead to serious deterioration in the health of the subject, that either resulted in: 
o A life threatening illness or injury 
o A permanent impairment of a body structure or a body function 
o In-patient or prolonged hospitalization 
o Medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
 
Lead to fetal distress, fetal death or congenital abnormality or birth defect.   
 
Medical and scientific judgment should be exercised in determining whether an event is an 
important medical event. An important medical event may not be immediately life-
threatening and/or result in death or hospitalization.  However, if it is determined that the 
event may jeopardize the patient and may require intervention to prevent one of the other 
outcomes listed in the definition above, the important medical event should be reported as 
serious. 
 
Examples of such events are intensive treatment in an emergency room for a 
bronchospasm or convulsions that do not result in hospitalization.  
 
This definition of an SAE is not intended to include hospitalization specifically to treat a 
condition that existed prior to the patient’s enrollment in the study (e.g., pre-existing knee 
injury that is surgically repaired during the study) or prearranged elective surgery performed 
during this study period.  
 
9.2 Unanticipated Serious Adverse Device Effect (USADEs): 
A serious adverse device effect which, by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report. 
 
 
9.3 Anticipated Adverse Events: 
As with any type of surgical procedure, there are certain risks or complications associated 
with shoulder resurfacing. The following list represents the most commonly reported 
complications and adverse events associated with surgery and shoulder replacement:   

 
 
 
 
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Potential risks associated with any surgery may include: 
 Pain  
 Bleeding  
 Blood clots 
 Infection  
 Swelling  
 Damage to surrounding blood vessels  
 Damage to surrounding tissues or nerves 
 Death 
Potential risks associated with any shoulder replacement may include: 
 Implant loosening  
 Implant movement 
 Implant wear  
 Allergic reaction to wear debris or implant materials 
 Implant fracture 
 Implant failure (including need to take the implant out) 
 Bone fracture 
 Shoulder dislocation 
 Shoulder pain 
 Loss of shoulder function 
 
9.4 Adverse Event Severity Determination: 
All Adverse Events must be classified by the investigator using mild, moderate, or severe to 
determine the level of severity of the AE as it relates to the evaluation of patient safety 
through the full course of the AE from initial reporting to the end of study for each patient 
who participates in this clinical study.  
 
ADVERSE EVENT SEVERITY 
Mild 
AE is noticeable to the patient but does not 
interfere with routine activity and does not 
require medical treatment. 
Moderate 
AE interferes with routine activity but 
responds to symptomatic therapy or rest.   

 
 
 
 
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Usually requires medical treatment. 
Severe 
AE that results in loss of life or limb. 
 
 
9.5 Adverse Event Reporting: 
Investigators and /or study staff are required to report AEs (and all reportable effects) per 
their Institutional Review Board/Ethics Committee Standard Operating Procedures. 
In the event of a complication, the Investigator and/or other professional personnel in 
attendance will undertake the appropriate therapy. All adverse signs and symptoms (device 
or procedure related) that occur during the study are to be recorded on an Adverse Event 
CRF.  The description of adverse events will include cause, date of initial onset, severity, 
treatment, and date of resolution. 
 
All serious and non-serious device or procedure related adverse events and unanticipated 
serious adverse device effects that occur during this investigation must be reported in a 
timely manner by the Investigator using either telephone or fax to: 
 
ATTN:  Clinical Research 
Ascension Orthopedics, Inc 
512-836-6933 
 
INCIDENT:  
Any malfunction or deterioration in the characteristics and/or performance of a device, as 
well as any inadequacy in the labelling or the instructions for use which, directly or 
indirectly, might lead to or might have led to the death of a patient, or USER or of other 
persons or to a serious deterioration in their state of health.” 
A serious deterioration in state of health can include:  
a) Life-threatening illness 
b) Permanent impairment of a body function or permanent damage to a body structure 
c) A condition necessitating medical or surgical intervention to prevent a) or b)  
(Examples:  - Clinically relevant increase in the duration of a surgical procedure 

 
 
 
 
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- A condition that requires hospitalisation or significant prolongation of existing 
hospitalisation) 
d) Any indirect harm as a consequence of an incorrect diagnostic or IVD test results when 
used within manufacturer´s instructions for use  
e) Foetal distress, foetal death or any congenital abnormality or birth defect 
 
Notification: 
As the product is CE marked and used in its intended purpose, Medical Device vigilance 
system applies: The Investigator should report incidents with Medical Device to the 
manufacturer or to the National Competent Authority, depending on national practice. 
 
 
10.0     Termination of Subject Participation 
  
 
Any subject who wishes to withdraw from this clinical investigation on his/her own accord 
and for whatever reason is entitled to do so without obligation and prejudice to further 
treatment.  In addition, the Clinical Investigator may decide for reasons of medical 
prudence (e.g. stroke, amputation), to withdraw a subject.  In either event, the Clinical 
Investigator will clearly document the date and reason(s) for the withdrawal on the 
Withdrawal CRF.  The investigator should note if the withdrawal was related to the device.  
 
11.0 Statistical Methods  
 
11.1 
Purpose 
 
This is an exploratory study intended to provide data that may be mined for a variety of 
purposes. The treatment of shoulder pathology with a prosthesis is an area where there is 
still a great deal to learn. There is no consensus, for example, regarding when a 
resurfacing is preferred to a total shoulder or hemi arthroplasty in subjects with an intact 
glenoid. 
Accordingly, the study is designed to allow comparisons to these implants either through 
literature review or other clinical data mined from outcome studies of other implant 

 
 
 
 
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configurations. The number of shoulders available must be adequate in number to follow 
outcomes in the long term, accounting for expected attrition, and in accordance with peer 
reviewed journal standards.  
  
11.2 
Study Design 
 
This clinical investigation is a prospective, non-comparative, multicenter, post market study 
designed to monitor the clinical safety and performance of the PyroTITANTM HRA  Shoulder 
prosthesis. Results will be contrasted with results from the literature.  
 
 
11.3 
Sample Size and Power Analysis 
 
The original sample size in this study was 150 enrolled subjects. Additional proof testing 
and improvements in the device inspection process were employed during the study, at 
which time it was determined that an additional cohort of subjects was necessary. We are 
now comparing a cohort of subjects enrolled after these changes to the original cohort of 
subjects. 
With an expected attrition rate of 10% per annum, this will yield an evaluable sample size of 
52 shoulders at ten years (150 * 0.910 = 52.3, where 0.9 or 90% is the number expected to 
be retained from one year to the next). Based on past experience, we may obtain clinical 
follow-up on this number of shoulders, but we may obtain radiographic follow-up on as few 
as two-thirds of these shoulders (about 35 shoulders). This remaining number of evaluable 
shoulders with clinical and radiographic follow-up is adequate to establish a reliable ten-
year survival estimate of survival for hemi arthroplasty (Dorey and Amstutz, 1986). 
For the new cohort, the sample size is calculated based on the non-inferiority of the study 
device.  The success rate for the study device is 96.1% from the original population and is 
used as reference rate. Therefore, for a conservative success rate of 96.1% of the study 
device is used in the study. The non-inferiority margin δ of -0.033 is chosen in the 
study.   212 subjects are required to achieve 100(1 – β) % =80% power to detect non-
inferiority at the Significance level of α = 0.05.   To account for 10% lost to follow-up, the 

 
 
 
 
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total number of additional subjects is 237.  Therefore, the estimated enrollment for the 
study will be 387 subjects. 
 
11.4 
Treatment Assignment 
All shoulders will be treated with PyroTITANTM HRA Shoulder prosthesis.  
   
11.5 
Interim Analysis 
 
Data will be reviewed for safety in an ongoing manner, according to standard formal 
procedures at Ascension Orthopedics. No interim analysis per se is planned; but it is 
anticipated that a number of outcomes will be followed through time; for example, surgical 
technique, and return to function. 
 
11.6 
Data Analysis    
Although this study is exploratory in nature, for many investigations the success of the 
implant will be a primary endpoint. 
 
11.7 
Primary Endpoint 
Clinical requirements for success will be evaluated at 24, 60 and 120 months: 
 Device remains implanted 
 Absence of device-related complications requiring surgical replacement, removal, or 
augmentation of components 
 Freedom from chronic dislocation 
 
11.8 
Secondary Endpoint  
Radiographic and MRI requirements for success at the different time points: 
 No  evidence of device failure, specifically progressive migration or implant 
loosening 
 Anatomic alignment is a criterion that may be included in the definition of success in 
some investigations 
Clinical outcomes measures at the different time points. 
 

 
 
 
 
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11.9 
Other Endpoints 
The following will be analyzed at the end of the trial: 
Adverse Events including, but not limited to:  
 Infection  
 Loss of fixation 
 Breakage 
 Dislocations 
 Revisions 
 
 
Data will be entered, verified and validated using a computer database system.  Both the 
data management and statistical analysis will be performed by Ascension Orthopedics, Inc.  
Descriptive statistics of patient demographic details will be calculated over all patients. Pre-
operative values of outcome variables will be compared to postoperative values at various 
time points. For interval level data, t-tests will be used; for ordinal level data (ranked data) 
the Wilcoxon matched-pairs signed-ranks test will be employed, and chi-square or Fisher’s 
exact tests will be used for categorical data. Correlation coefficients may also be employed 
to determine whether preoperative variables are related to outcome variables. 
 
12.0  Risk Analysis 
 
Radiographs are a normal part of post-operative follow up and the subject will experience 
no additional radiation exposure beyond what is clinically necessary.  The radiation 
exposure risk is estimated to be 0.004mSv per follow-up interval with 8 intervals in the 
study.  This is comparable to 36 days exposure to natural background radiation.   The 
radiation exposure risk is based on an X-ray to the upper extremity which has a radiation 
exposure of 0.001mSv per x-ray.  Muscle discomfort and/or shoulder joint pain may occur 
during the musculoskeletal muscle strength and range of motion testing. The patient will be 
informed that rest and ice should be applied. Additional concerns should be directed 
towards the treating surgeon for consultation. PyroTITANTM HRA Shoulder prosthesis risks, 

 
 
 
 
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that are no different from other prosthesis, include infection, failure of prosthesis, implant 
loosening, or shoulder dislocation and/or subluxation.  The patient will be told this during 
the normal pre-surgical information process and sign an Informed Consent related to the 
surgical procedure acknowledging this information. Any complications can be treated with 
conversion to total shoulder arthroplasty, reverse shoulder arthroplasty, or shoulder 
arthrodesis (fusion). 
The benefits of shoulder resurfacing surgery depend upon each patient.  Benefits usually 
include a conservation of humeral bone, reduction or relief of pain, restoration or 
improvement in range of motion and mobility, correction or improvement of disfiguring 
deformity and an improvement in the patient’s quality of life.  Participation in this study may 
benefit society as well as provide valuable information to the orthopaedic community other 
doctors and help them make informed decisions about the kind of shoulder replacement 
components most likely to benefit their patients. The patients will benefit by becoming 
better informed of the status of their shoulder or injury. They will have added contact with 
their surgeon and his or her staff.  The patient will also be informed of the status of the 
Pyro-Titan Resurfacing Shoulder prosthesis during their follow-up examination assessment 
visits. Results of this study will provide information about the effect of Pyro-Titan 
Resurfacing Shoulder prosthesis on the functional outcomes experienced by the subjects 
post shoulder arthroplasty. 
 
 Minimal risks are associated with this study.   Subjects may experience infection, failure of 
prosthesis, glenoid wear, implant loosening, or dislocation post PyroTITANTM HRA  Shoulder 
prosthesis implant. The risks of harm anticipated in the proposed research are not greater, 
considering probability and magnitude of those ordinarily encountered in shoulder arthroplasty 
or during the performance of routine physical and psychological examinations or tests.  The 
patient may or will experience changes in function, pain, and satisfaction levels of activities of 
daily living.  The other alternative is to continue with their current levels of satisfaction, 
function and pain as related to the shoulder arthritis. 
 
Any surgical procedure poses a potential risk and the procedures undertaken as part of this 
clinical investigation are no exception.  There are known risks associated with the method 

 
 
 
 
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of anesthesia (general, epidural, spinal). Separate consent forms will be presented to 
subjects outlining the risks of shoulder surgery and anesthesia. In addition to these there 
are risks associated with a surgical procedure that involves a device, including the 
following: damage to nervous and vascular tissue, infection, long term swelling, fracture of 
bone surrounding the device, loosening, dislocation or fracture of the device, hemorrhage, 
decrease in range of motion or mobility deformity, allergic reaction to the device and failure 
of the device to be incorporated into the body.  A complication may require revision 
surgery.  Very rarely a complication may prove fatal.  This clinical trial of the CE marked 
(November 30th, 2009)PyroTITAN™ HRA Shoulder prosthesis, used according to this 
protocol and labeling indications, poses no additional risks over those normally associated 
with shoulder resurfacing arthroplasty. 
   
13.0 Device Descriptions 
 
The Ascension® PyroTITAN ™ HRA device is an anatomically designed, semi-constrained, 
monolithic device designed for resurfacing of the humeral head (hemi-shoulder).  The system 
is designed for non-cemented (i.e. press-fit) fixation.  Each device is boxed individually and 
delivered sterile for single use.  The system incorporates twelve anatomically designed sizes.  
Head sizes are identified using width and height (in millimeters) and are as follows:  38/14, 
41/15, 41/18, 44/16, 44/19, 47/17, 47/20, 50/18, 50/21, 53/19, 53/22 and 56/21.  The Pyro 
TITANTM HRA device incorporates design features for replacing the damaged humeral head 
bearing surface and restoring normal anatomy with minimal bone resection.  The stem is 
tapered with a cruciform shape to provide rotational as well as axial stability of the seated 
implant.  System instrumentation is designed to offer precise implant preparation.  Device 
components are provided sterile in packaging containing a single component. 
 
 
 
 
 
 

 
 
 
 
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14.0 Investigator Responsibility 
 
Prior to the initiation of this clinical investigation, the Clinical Investigator will approve this 
CIP by signing a research agreement.  This signature confirms that the clinical investigation 
will be performed in compliance with the CIP. 
 
All Investigators are responsible for maintaining a complete case history for each Subject.  
This case history must be adequately detailed to cover all data points on the Case Report 
Forms.  Worksheets may be developed and implemented to simplify this process, or it is 
expected that detailed dictations will be done.  The case history is defined as the “source 
documentation.” 
 
Each Investigator and all personnel from the investigational site will maintain records of all 
correspondence, electronic, written, and verbal, relating to any aspect of the clinical 
investigation. The records are maintained in the Investigator’s Regulatory Binder consisting 
of, but not limited to correspondence with other participating clinical investigators, the 
reviewing ETHICS BOARD, and the Sponsor. The study monitor will examine the contents 
of the correspondence file as part of the monitoring visit. 
 
Prior to the investigational site beginning Subject enrollment, the following documents will 
be fully executed and returned to Ascension Orthopedics by the clinical investigators: 
 Curriculum vitae (c.v.)  
 Medical license  
 Confirmation of ETHICS BOARD Approval 
 Clinical Research Agreement 
 Investigator Compensation Agreement 
 Financial Disclosure  
 
Copies of the Investigator Agreement will be provided by the Sponsor after contracting. 
 

 
 
 
 
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14.1   Investigator Regulatory Binder 
 
Each investigator must maintain an accurate, complete, and current copy of the 
Investigator Regulatory Binder. Upon receipt of copies of changes or revision updates to 
the Investigator Regulatory Binder(s) from the Sponsor, the Investigator or designee will 
add the updated document to the Regulatory Binder and will mark the outdated portion of 
the Regulatory Binder as “obsolete” by crossing a diagonal line across the page(s) along 
with date the page was obsoleted and the initials of the person performing the update. The 
outdated pages will be removed from their current section and filed in the “Obsoleted” 
section.  The study monitor will examine the contents of the Investigator Regulatory Binder 
as part of the monitoring visit. 
 
14.2 Case Report Form Completion 
 
Data will be transposed onto the CRF’s or data collection form.  Data will be accurately and 
completely recorded in ink on the CRF’s or electronically on the data collection form.  Prior 
to submission to Ascension, any errors on the forms are to be corrected, either crossed out 
with a single stroke, initialed and dated on the paper form or by verification and reentry of 
electronic data.  Typing correction fluid must not be used.   After submission to Ascension, 
no changes may be made to the data collection form.  Instead, a Data Clarification Form 
(DCF) must be used to document any modifications to a data collection form.  The signed, 
original DCF is submitted to Ascension and a copy is affixed to the original, corresponding 
CRF.  The personal data recorded on all documents will be regarded as confidential.  The 
Clinical Investigator will be responsible for the timing, completeness, and accuracy of the 
data collection form and will retain a copy of each completed form.   
 
The Investigator’s copies of the Investigation, including Consent forms and CRF’s should 
be held for a minimum of fifteen years after the completion of the investigation.  In the event 
the Clinical Investigator retires or moves, the investigator will provide the name and 
address of the custodian of the study records.  Alternatively the custody of the study 
records may be transferred to the Sponsor with notification to the governing Ethics Board. 

 
 
 
 
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The subjects’ participation in the investigation must be recorded in the Subject’s hospital 
notes.  In addition, the Investigator must keep a  separate list of all subjects entered into 
clinical investigation.  This list should include the name, date of birth, and subject number. 
 
 
15.0    Institutional Review Board (ETHICS BOARD) Action 
 
This study is intended to monitor post-market clinical outcomes of the devices described 
above.  The Notified Body has cleared all devices utilized in this evaluation for general use 
in accordance with printed indications. It is the responsibility of the investigator to submit a 
copy of the investigational plan and secure approval of the governing ETHICS BOARD for 
each institution under consideration for the study.  If ETHICS BOARD approval is not 
required, this must be indicated in a signed letter from the governing ETHICS BOARD. 
 
 No subjects should be consented or requested to complete a release of medical records 
until ETHICS BOARD approval has been obtained.  It is the responsibility of the 
investigator to comply with governing ETHICS BOARD requirements including but not 
limited to reporting adverse events, reporting consent and protocol deviations, submission 
of periodic reports in a timely manner and any other institutional, state or federal 
regulations.  
 
16.0   Informed Consent 
 
Informed consent materials, including a model consent form; will be provided to each 
investigator.  In compliance with Ascension Orthopedics, Inc. policy, no subject is to be 
enrolled in this study without adequate informed consent being provided or a waiver of 
consent granted by the ETHICS BOARD.  The informed consent process should be 
documented in the subject’s medical record.  Failure to obtain, or improper documentation 
of, informed consent is in violation of Ascension policy and the study protocol unless 

 
 
 
 
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exempted by an ETHICS BOARD waiver. In the event of such an exemption, a release of 
Medical Records shall be obtained. 
 
Some ETHICS BOARD’s require modifications to the Informed Patient Consent form (IPC) 
to satisfy specific institutional requirements. Use of modified consent forms is permitted 
provided they meet the local requirements.   
 
The investigator will solicit the informed consent of any patient meeting the selection criteria 
prior to surgery.  The investigator will answer all questions the subject may have and will 
explain the following features of the study thoroughly including: 
 
 The purpose of the study 
 Possibility of failure and subsequent treatment(s) 
 Alternative procedures 
 Requirements of the study (follow-up visits), 
 All of the Subject’s rights as a subject in the clinical investigation. 
 
 
If the patient agrees to participate in the study, either an IPC form as approved/required by 
each ETHICS BOARD or a release of medical records as appropriate must document this.  
One completed copy of the consent and/or release form is to be given to the patient, 
another placed in the hospital files if required.  The original IPC form remains with the 
clinical investigator (i.e., within the CRF booklet or clinic chart).  The IPC is not forwarded 
to the Sponsor. Once a Subject has executed the IPC documentation, they are considered 
a study subject. 
 
Subject should sign and date the IPC form prior to any study required assessments or 
exams as described in Section 6.0 above, and prior to the day of surgery. However, if the 
IPC is signed on the day of surgery, then the source document must state that the subject 

 
 
 
 
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was given adequate time prior to the time of surgery to review and give consent. In such a 
case, the time the Subject signed the IPC form must be documented.  
 
For the purposes of this study, the success or failure of the Product will be based upon the 
patient’s clinical results as measured using the clinical and radiographic parameters 
detailed herein.  Investigators should document each death using the Adverse 
Event/Withdrawal CRF.  
 
17.0 Review of Source Documents 
 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  
Source data are contained in source documents   Examples of these original documents, 
and data records include: hospital records, clinical and office charts, laboratory notes, 
patient completed evaluation forms, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, magnetic media, 
x-rays, subject files, and records kept, at the laboratories, and at technical departments 
involved in the clinical trial. 
 
The Investigator is responsible for ensuring that the data on the case report forms is 
consistent with the data in the source documentation.  The Investigator may designate a 
medically trained designee to sign all forms except the Withdrawal form and the Adverse 
Event form.  The Investigator must make source documentation available for monitoring by 
the Sponsor or delegate, the ETHICS BOARD, and other authorized government agencies.   
Failure or unwillingness to provide this access will disqualify the site and Investigator from 
participation in this clinical evaluation.  
 
18.0  Record of Device Inventory 
 
This is a post market study and all devices are CE marked.  Therefore inventory control is 
not a regulatory requirement.  
 
 

 
 
 
 
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19.0 Sponsor Obligations 
 
19.1   Investigator Training 
 
All participating investigators will undergo training on the PyroTITANTM HRA Shoulder 
prosthesis either through a hands-on training session or by a Sponsor approved training 
module. 
 
19.2   Monitoring 
 
The Sponsor will designate qualified individuals to monitor the progress of the clinical 
investigation.  The monitor(s) responsibilities include: 
 Visiting the Investigator periodically to ensure the fulfillment of all obligations 
associated with the clinical investigation. 
 Reviewing individual Subject records and other supporting source documentation, 
comparing those records with CRFs prepared by the Investigator and submitted to 
the Sponsor, and ensuring that data submitted to the Sponsor is accurate and 
complete. 
 Maintaining a record of each on-site visit to an Investigator noting findings, 
conclusions, and actions taken to correct deficiencies. 
 
 
19.3   Sponsor Study Termination 
 
Both the sponsor and the Investigator reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange the procedures on an individual study 
basis after review and consultation. In terminating the study, Ascension Orthopedics and 
the Investigator will assure that adequate consideration is given to the protection of the 
patient’s interests. 
 
 

 
 
 
 
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20.0   Changes to Investigational Plan 
 
No changes to this protocol with the exception of those of an emergent nature will be made 
without written consent from the sponsor and mutual agreement between the investigators 
and sponsor.  The investigators, sponsor, and investigators’ governing ETHICS BOARD 
will record all changes. 
 
Applicable ETHICS BOARD approval will be obtained prior to implementation of changes in 
the Investigational Plan that may affect the scientific soundness of the investigation, or the 
rights, safety, or welfare of study subjects. 
 
 
21.0   Confidentiality 
 
Information about study subjects will be kept confidential and managed according to the 
requirements of the country of the participating clinical investigator. 
Data protection and data transfer 
In order to observe the confidentiality of personal data, each patient will be allocated a 
confidential identification code consisting of the investigator centre number and a 3 figures 
patient number. 
CRF or other documents submitted to the sponsor will identify a patient by this identification 
code. Each investigator will keep in his file a screening Log and a patient identification list 
(including complete name and date of birth of each patient). To allow compliance with GCP 
principles, each patient will be asked for consent regarding the access to source 
documents for monitoring, audits, and inspections.  
The Information Letter and Data Transfer Authorization form explain that the study data will 
be kept in an electronic form, confidentially, in accordance with the French law N°78-17. All 
the computerised data will be identified by "centre n°/ patient n°". 

 
 
 
 
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The information Letter and Data Transfer Authorization Form will specify that the sponsor 
representative and the competent authorities will have direct access upon request to the 
source documents related to the study, including medical antecedents, to check the 
accuracy of the data. 
Study documents and records will be kept for at least 15 years after the end of the study by 
the investigator: this includes codes allowing the identification of patients, medical files and 
all the source data, the CRF, the queries, the patient's information letter and DTA, the 
copies of IEC and competent authorities approval (if necessary) and any other document 
pertinent to the study. 
Integra LifeSciences Corp. will store all of the documents relating to the study throughout 
the lifespan of the product and for a minimum of 15 years: 
- The text of the clinical protocol and its annexes; 
- The EC opinion; 
- The case report forms; 
- The anonymised data in a database; 
- The monitoring documents (correspondence, memos, etc.) 
 
22.0   Withdrawal or Termination of the Clinical Investigation 
 
Any subject who wishes to withdraw from this investigation on his/her own accord and for 
whatever reason is entitled to do so without obligation and prejudice to further treatment. In 
addition, the Investigator may decide for reasons of medical prudence, to withdraw a 
subject. In either event, the Investigator will clearly document the date and reason(s) for the 
subject’s withdrawal from this investigation in the clinic notes and should indicate whether 
or not he considers it related to the device. 
Both the sponsor and the Investigator reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange the procedures on an individual study 
basis after review and consultation. In terminating the study, Ascension Orthopedics and 
the Investigator will assure that adequate consideration is given to the protection of the 
patient’s interests. 
 

 
 
 
 
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Protocol Date: May 27, 2013               
 
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APPENDIX A 
CASE REPORT FORMS