Intraoperative Case Series Study: Trial Rasp Position Versus SL-PLUS™ MIA Ti/HA Femoral Hip Stem Position
Conditions: Osteoarthritis
Sponsor: Smith & Nephew Orthopaedics AG

 
 
 
Intraoperative case series study: trial rasp position versus SL-PLUS™ MIA 
Ti/HA femoral hip stem position 
 
 
 
Protocol Number:  
 
15-4567-03 
Protocol Date:  
 
07 Sep 2015 
Protocol Version: 
 
1.0 
Study Product Name: 
 
SL-PLUS™ MIA Ti/HA femoral hip stem 
Sponsor:     
 
 
Smith & Nephew Orthopaedics AG 
 
 
 
 
 
 
Oberneuhofstrasse 10d                  
 
 
 
 
6340 Baar   
 
 
 
 
Switzerland 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
                      
 
 
 
 
 
Nondisclosure Statement 
This document contains information that is confidential and proprietary to Smith & Nephew PLC and 
Smith & Nephew, Inc. and is intended for use only by Smith & Nephew and its manufacturers. It shall 
not be reproduced or copied in whole or in part, nor shall the contents be disclosed by any mean 
without prior written permission from Smith & Nephew, nor shall anyone make any use of it that is 
contrary to the expressed or implied wishes of Smith & Nephew. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Table of Contents 
 
ABBREVIATIONS & DEFINITIONS .................................................................................................................................................... 4 
PROTOCOL SYNOPSIS ................................................................................................................................................................. 5 
1. 
BACKGROUND AND STUDY RATIONALE ............................................................................................................................... 6 
2. 
STUDY OBJECTIVES .......................................................................................................................................................... 7 
2.1. 
Primary Endpoint......................................................................................................................................................... 7 
2.2. 
Secondary Endpoints ................................................................................................................................................. 7 
3. 
STUDY DESIGN ............................................................................................................................................................... 8 
4. 
STUDY DEVICE ................................................................................................................................................................ 8 
4.1. 
Surgical Technique ..................................................................................................................................................... 8 
4.2. 
Device Accountability ................................................................................................................................................. 8 
5. 
STUDY POPULATION ........................................................................................................................................................ 9 
5.1. 
Subject Screening & Enrollment ................................................................................................................................ 9 
5.2. 
Subject Inclusion Criteria ........................................................................................................................................... 9 
5.3. 
Subject Exclusion Criteria ........................................................................................................................................... 9 
6. 
STUDY PROCEDURES ...................................................................................................................................................... 10 
6.1. 
Study Schematic ....................................................................................................................................................... 10 
6.1.1. Assessment 1: Pre-Operative Visit ........................................................................................................................... 11 
6.1.2. Assessment 2: Surgery ............................................................................................................................................. 11 
7. 
SUBJECT COMPLETION AND DISPOSITION ......................................................................................................................... 12 
7.1. 
Screening .................................................................................................................................................................. 12 
7.2. 
Enrollment ................................................................................................................................................................. 12 
7.3. 
Conditions for Study Termination ............................................................................................................................ 12 
8. 
SAFETY REPORTING ........................................................................................................................................................ 13 
8.1. 
Definitions for safety reporting ................................................................................................................................ 13 
8.2. 
Safety: Investigator’s Responsibilities ..................................................................................................................... 14 
8.3. 
Timelines for Submission of Safety Information: .................................................................................................... 15 
8.4. 
Safety reporting: Sponsor’s Responsibilities .......................................................................................................... 15 
9. 
STATISTICAL PROCEDURES .............................................................................................................................................. 16 
9.1. 
Hypothesis and Sample size calculation ................................................................................................................ 16 
9.2. 
Statistical Analysis .................................................................................................................................................... 16 
9.2.1. Primary Endpoint Analysis ........................................................................................................................................ 17 
9.2.2. Secondary Endpoint Analysis ................................................................................................................................... 17 
9.3. 
Missing Data .............................................................................................................................................................. 17 
10. 
ETHICAL CONSIDERATIONS ............................................................................................................................................. 18 

 
 
 
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10.1. Ethical Approval ........................................................................................................................................................ 18 
10.2. Protocol Amendments .............................................................................................................................................. 18 
10.3. Informed Consent ..................................................................................................................................................... 18 
10.4. Risk – Benefit Analysis ............................................................................................................................................. 18 
11. 
MONITORING PROCEDURES ............................................................................................................................................ 19 
11.1. 
Source Documentation............................................................................................................................................. 19 
11.2. Direct Access ............................................................................................................................................................ 19 
11.3. Site Qualification Visit (SQV) .................................................................................................................................... 19 
11.4. Prior to Study Initiation ............................................................................................................................................. 19 
11.5. Site Initiation Visit (SIV) ............................................................................................................................................. 19 
11.6. Interim Monitoring Visits (IMVs) .............................................................................................................................. 20 
11.7. 
Sponsor Audits and Regulatory Inspection ............................................................................................................ 20 
11.8. Close Out Visit (COV)............................................................................................................................................... 20 
11.9. Documentation of Site Visits ................................................................................................................................... 20 
11.10. Data Handling and Record Keeping Requirements ............................................................................................... 20 
11.11. Data Recording and Record Retention ................................................................................................................... 20 
12. 
DEVIATIONS FROM PROTOCOL ......................................................................................................................................... 21 
12.1. Protocol Deviation Reporting Requirements ........................................................................................................... 21 
13. 
PUBLICATION POLICY ...................................................................................................................................................... 21 
13.1. Multicenter Publication ............................................................................................................................................. 21 
13.2. Investigator Publication ............................................................................................................................................ 21 
13.3. Authorship ............................................................................................................................................................... 22 
BIBLIOGRAPHY ......................................................................................................................................................................... 23 
 
 
 

 
 
 
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ABBREVIATIONS & DEFINITIONS 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
AP  
Anterior-posterior 
ASIS 
Anterior Superior Iliac Spine 
CAPA 
Corrective and Preventive Action  
CCD angle 
Caput-collum-diaphyseal angle 
COV 
Close Out Visit 
CRF 
Case Report Form 
EC 
Ethics Committee  
FDA 
Food and Drug Administration  
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IFU 
Instructions for Use 
IMV 
Interim Monitoring Visit 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SIV 
Site Initiation Visit 
SQV 
Site Qualification Visit 
THA 
Total Hip Arthroplasty 
USADE 
Unanticipated Serious Adverse Device Effect  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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PROTOCOL SYNOPSIS 
Title of Study: 
Intraoperative case series study: trial rasp position versus SL-PLUS™ MIA Ti/HA femoral 
hip stem position 
Study Type: 
 
Post-market, Evidence collection 
Study Device: 
SL-PLUS™ MIA Ti/HA femoral hip stem 
Indications: 
• 
Advanced hip joint wear due to degenerative, post-traumatic or rheumatoid 
arthritis 
• 
Fracture or avascular necrosis of the femoral head 
• 
Follow-on conditions after previous surgery such as osteosynthesis, joint 
reconstruction, arthrodesis, hemiarthroplasty or total hip replacement. 
Study design: 
Observational, single arm, prospective, multi-center, case series study 
Study Objective: 
The study objective is to evaluate if there is a difference between the position of the last 
trial rasp and the final implant position of the SL-PLUS™ MIA Ti/HA femoral hip stem. 
Primary Endpoint: 
Mean difference between the position of the last trial rasp and the final implant position 
as measured by an intraoperative fluoroscopic measurement 
Secondary Endpoints: 
Discrepancy of leg length after total hip arthroplasty 
Intraoperative complications 
Length of Study: 
3 months enrollment period = total study duration 
Number of Sites: 
up to 4 sites 
Sample Size: 
40  
Inclusion Criteria: 
Subject: 
• 
requires primary THA with the SL-PLUS™ MIA Ti/HA femoral hip stem 
• 
is at least 21 years of age at the time of surgery  
• 
is skeletally mature in the PI’s judgement 
• 
has consented to participate in the study by signing the Ethics Committee (EC) 
approved Informed Consent Form (ICF) 
Exclusion Criteria: 
Subject: 
• 
requires the use of a ceramic-on-ceramic bearing 
• 
has infections, acute or chronic, local or systemic 
• 
has severe muscle, nerve or vascular diseases that endanger the respective 
limb 
• 
has lack of bone substance or defective bone quality that jeopardizes the 
stable seating of the prosthesis 
• 
has any concomitant disease that may jeopardize implant function 
• 
has a known allergy to study device or one or more of its components 
• 
requires a revision surgery and has extensive bone defects 
• 
has diagnosis of an immunosuppressive disorder 
• 
is pregnant  

 
 
 
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1. 
BACKGROUND AND STUDY RATIONALE  
As the incidence of joint disease continues to increase, an ever growing percentage of the affected population 
will undergo total hip arthroplasty (THA). With increasing life expectancy the demand on these hip arthroplasties 
is rising [1]. 
The success of the hip implant is directly linked to the correct position of the femoral stem. A malposition of the 
femoral stem may cause leg length differences, tension problems, increased risk of luxation, increased risk of 
impingement and increased wear which may be followed by early loosening. 
Konyves et al. examined leg length inequality in 90 patients after THA. 62% of patients were observed having a 
leg length discrepancy after THA being associated with back pain, gait disorders and following general patient 
dissatisfaction. The authors further showed that in 98% of patients with leg length discrepancy, the discrepancy 
occurred in the femoral component strengthening the importance of appropriate placement of the femoral 
component [2]. 
The correct position of an uncemented hip stem is planned preoperatively. During surgery, the final position of 
the rasp should correspond to the preoperatively determined position and the same position should be adopted 
by the uncemented femoral stem [3]. 
Barink et al. examined this rasp-stem correspondence for two different rasp-stem systems in a laboratory study. 
They observed an average rasp-stem mis-match in three orthogonal directions smaller than 2mm for both the 
CLS system (Centerpulse/Zimmer Warsaw, IN, USA) and the CBC-T system (Mathys, Bettlach, CH). Based on 
good long term results documented for the CLS system, the authors considered the measured difference as 
being of very low clinical relevance [3]. 
In contrast, Hozack et al. showed that malpositioning of the stem is not a rare event in real life surgeries. Hozack 
et al. showed by observation of 100 uncemented THA with the modular Taperloc prosthesis (Biomet, Warsaw, IN, 
USA) that the preoperatively planned stem position could not be achieved for all cases. In 19 cases the neck 
length needed to be adapted after insertion of the femoral stem to achieve stability or avoid a leg length 
difference [4].  
As indicated by Hozack et al., femoral malposition can be corrected to some degree by the selection of the 
appropriate components when using a modular hip system. Possibilities for correction of femoral malposition are 
more limited when using a mono-block system. Although small differences in the position between the final rasp 
and the stem are not of clinical significance, femoral malpositioning should be avoided to the highest degree 
possible as it forms a potential source of clinical complications [3]. 
 
The SL-PLUS™ MIA Ti/HA femoral hip stem is a dual-tapered straight stem with a rectangular cross section. The 
SL-PLUS™ MIA Ti/HA stem belongs to the SL-PLUS™ family and is based on the SL-PLUS™ standard stem. 
The Ti/Ha coating causes an oversize of 0.7mm compared to the size of the rasp which might prevent the 
implant from being inserted as deeply as the rasp [5].  
The purpose of this study is to evaluate if there is a difference between the final position of the femoral stem and 
the last trial rasp when using the SL-PLUS™ MIA Ti/HA femoral hip stem with the appropriate set of instruments. In 
case a difference is detected this study also serves to quantify the difference in rasp and stem position for the 
SL-PLUS™ MIA Ti/HA femoral hip stem.  
 
 
 
 
 
 
 

 
 
 
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2. STUDY OBJECTIVES 
The study objective is to evaluate if there is a difference between the femoral position of the last trial rasp and 
the final implant position of the SL-PLUS™ MIA Ti/HA femoral hip stem. 
 
2.1. Primary Endpoint  
The primary endpoint is the mean difference D between the position of the last trial rasp and the final implant 
position of the SL-PLUS™ MIA Ti/HA femoral hip stem. The difference D is determined by analyzing standardized 
fluoroscopic images taken during surgery. 
 
The difference D is given in mm and is defined as D = x1 – x2 with x1 being the distance between the shoulder of 
the trial rasp and the tip of the greater trochanter and x2 being the distance between the shoulder of the implant 
and the tip of the greater trochanter. 
The distance to be measured is shown in Figure 1: Example of pre-operative planning. 
 
 
Figure 1 Pre-operative planning: x = distance between shoulder of implant and the tip of the greater 
trochanter [mm] 
The diameter of the trial head and the final ball head will be measured to calibrate the size of the digital image. 
 
The study hypothesis is defined as: 
H0:  
The null hypothesis is that there is no mean difference between the position of the last trial rasp and 
the final implant position of the SL-PLUS™ MIA Ti/AH femoral hip stem. 
H1:  
The alternative hypothesis is that there is a mean difference between the position of the last trial rasp 
and the final implant position of the SL-PLUS™ MIA Ti/AH femoral hip stem. 
 
2.2. Secondary Endpoints  
The secondary endpoints include a measurement of leg length discrepancy preoperatively and after insertion of 
the SL-PLUS™ MIA Ti/HA femoral hip stem. In addition, intraoperative complications will be collected. 
 
 
 

 
 
 
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3. STUDY DESIGN 
This is an observational, single arm, prospective, multi-center, case series study to collect intraoperative data 
from 40 subjects implanted with the SL-PLUS™ MIA Ti/HA femoral hip stem at 4 sites in Europe. 
Data from eligible subjects, who have provided written and informed consent for the collection of their coded 
data, will be recorded on specially designed case report forms (CRFs). 
No follow-up visits after surgery are planned for study participants. Therefore, total study duration for study 
participants is completed with surgery. 
 
A final data analysis describing the study outcome is planned after completion of study assessments. 
 
4. STUDY DEVICE 
The SL-PLUS™ MIA Ti/HA femoral hip stem is a dual-tapered straight stem with a rectangular cross section. The 
SL-PLUS™ MIA Ti/HA stem belongs to the SL-PLUS™ family and is based on the anchorage principles of the SL-
PLUS™ stem. 
The SL-PLUS™ MIA Ti/HA stem has a minimal invasive surgery-friendly design allowing the rasps and the stem to 
be introduced into the bone in a curved manner. This allows reduction of bone resection in the trochanteric 
region, minimizes the risk of fracture, maximizes preservation of the tendon insertions and protects muscles and 
skin. 
The SL-PLUS™ MIA Ti/HA stem has a Ti/HA multi layer coating in the proximal area of the stem leading to 
accelerated and increased bone on-/in- growth with the aim of avoiding development of radiolucent lines by 
enhancement of load transmission in the metaphyseal region. 
 
The SL-PLUS™ MIA Ti/HA stem is made from Ti6AI7Nb Titanium Aluminium Niobium alloy. Two offset options are 
available. The standard stem is available with a Caput-collum-diaphyseal angle (CCD) of 131° and the lateral stem 
is available with a CCD angle of 123°. 
The standard stem is available in 128mm to 188mm length. The lateral stem is available in 136mm to 188mm 
length. 
 
4.1. Surgical Technique 
All study related procedures with the SL-PLUS™ MIA Ti/HA femoral hip stem must be performed according to the 
recommended surgical technique described in the labeling and in the instructions for use (IFU). 
Surgeons selected to participate in this study will be familiar with implanting SL-PLUS™ MIA Ti/HA femoral hip 
stem and have evidence of training and expertise in the study procedure.  
 
4.2. Device Accountability 
Device accountability is not required to be recorded as sites will be expected to use products from their own 
stock. Device information will be recorded on the CRF and chart sticks will be kept within the CRF to document 
the devices used. 
 
 

 
 
 
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5. STUDY POPULATION 
 
5.1. Subject Screening & Enrollment 
To eliminate the potential for selection bias, Investigators should consecutively pre-screen all subjects 
undergoing THA with the SL-PLUS™ MIA Ti/HA femoral hip stem. In order to do so, only the existing information 
obtained per standard routine medical procedures will be used. No study-specific screening procedures, 
activities or questionnaires will be performed during pre-screening. 
Once a subject has completed the informed consent procedure and signed the Informed Consent Form (ICF), the 
Principal Investigator (PI) or delegated study research staff can complete the screening process with the subject. 
All potential subjects who undergo the screening process will be documented on a Screening and Enrollment Log, 
on which reasons for exclusion from or denial to participate should be noted. 
 
5.2. Subject Inclusion Criteria 
Subject: 
• 
requires primary THA with the SL-PLUS™ MIA Ti/HA femoral hip stem 
• 
is at least 21 years of age at the time of surgery  
• 
is skeletally mature in the PI’s judgment 
• 
has consented to participate in the study by signing the EC approved ICF 
 
5.3. Subject Exclusion Criteria 
Subject: 
• 
requires the use of a ceramic-on-ceramic bearing 
• 
has infections, acute or chronic, local or systemic 
• 
has severe muscle, nerve or vascular diseases that endanger the respective limb 
• 
has lack of bone substance or defective bone quality that jeopardizes the stable seating of the 
prosthesis 
• 
has any concomitant disease that may jeopardize implant function 
• 
has a known allergy to study device or one or more of its components 
• 
requires a revision surgery and has extensive bone defects 
• 
has diagnosis of an immunosuppressive disorder 
• 
is pregnant  
 
 

 
 
 
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6. STUDY PROCEDURES 
6.1. 
Study Schematic 
The study duration for each subject is defined as the time between signing the ICF and time of completion of 
surgery (transfer to general ward). The intervals and schedule of events are provided in Table 1. 
Table 1 Schedule of events 
Schedule of events 
Pre-Operative 
Surgery /  
Peri-Operative 
Patient Information and Informed Consent 
√ 
 
Inclusion/Exclusion Criteria 
√ 
 
Demographics/Medical  History 
√ 
 
Radiographic assessment 
√ 
 
Operative Data Collection 
 
√ 
Fluoroscopic assessment 
 
√ 
Measurement of leg length discrepancy 
√ 
√ 
Adverse Event Assessment 
√* 
√ 
End of Study/Exit   
 
√ 
*if applicable 
The following algorithm should guide through the steps of pre-screening, screening, enrollment and study 
conduct in accordance with sections 6 Study Procedures and 7 Subject Completion and Disposition of this 
protocol. 
 
Figure 2 Overview of pre-screening, screening, enrollment and study conduct 

 
 
 
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6.1.1. 
Assessment 1: Pre-Operative Visit 
During the pre-operative visit a standard anterior-posterior (AP) pelvic hip radiograph will be taken. 
The AP view should include full pelvic overview. The pre-operative radiograph will be taken for diagnostic 
purposes and THA planning. The Investigator will analyze the pre-operative radiograph and collect the following 
information on the appropriate CRF: 
 
- 
diagnosis for THA 
- 
bone quality according to Dorr et al. [6] 
- 
distance x between the shoulder of the implant and the tip of the greater trochanter, reference Figure 1, 
measured during preoperative planning 
Based on the pre-operative planning, implant sizes planned to be used during THA will be recorded on the CRF. 
The leg length difference will be measured by the Investigator or designee during the preoperative physical 
examination. The length of each lower extremity is determined in cm by measuring the distance between the 
anterior superior iliac spine (ASIS) and the medial malleolus by using a measuring tape with the subject in supine 
position [7]. Measured distances will be recorded on the appropriate CRF. 
 
6.1.2. 
Assessment 2: Surgery 
During surgery two fluoroscopic AP images will be taken showing the position of the final trial rasp with trial head 
and the final position of the implanted stem with final ball head. The joint will be reduced at the time the images 
are taken. The AP view should include the full articulation of the operated side with the greater trochanter and 
the shoulder of the implant / rasp visible. 
The images will be de-identified and submitted to an assigned medical person for centralized analysis after 
surgery. The medical person will be assigned by S&N to analyze the fluoroscopic images and to collect the 
following information on the appropriate CRF: 
 
- 
distance x1 between the shoulder of the trial rasp and the tip of the greater trochanter 
- 
distance x2 between the shoulder of the implant and the tip of the greater trochanter 
- 
diameter of trial head and final ball head 
In addition, the following data will be collected during surgery and recorded on the appropriate CRF: 
 
- 
It will be recorded what type of rasping instrument was used for femoral preparation giving the following 
options: 
o 
Slap hammer 
o 
Woodpecker 
o 
Mallet 
o 
Combination 
- 
Information of implanted devices will be recorded on the CRF and by collecting the chart sticks on the 
CRF. 
- 
The type of the surgical approach will be collected. 
- 
During surgery it will be recorded if the surgeon needed to correct the position of the stem compared to 
the final rasp and which one of the following methods was used: 
o 
Smaller ball head length 
o 
Larger ball head length 
o 
Removal of stem and enlargement of femoral bed with last trial rasp 
o 
Other methods 
All intraoperative complications will be recorded as outlined in section 8 Safety reporting. 

 
 
 
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The leg length difference will be measured by the Investigator or designee peri-operatively shortly after surgery 
before transfer of the subject to the general ward. The length of each lower extremity is determined in cm by 
measuring the distance between the ASIS and the medial malleolus by using a measuring tape with the subject 
in supine position. Measured distances will be recorded on the appropriate CRF. 
 
7. SUBJECT COMPLETION AND DISPOSITION 
7.1. Screening  
Patients considered potential candidates for the study based on the Investigator’s initial assessment (pre-
screening) must sign an EC approved ICF prior to any study activities. The PI or delegated study research staff 
will review the eligibility criteria and if determined as eligible will complete the first study assessment 
(Assessment 1: pre-operative visit) with the subject. 
 
7.2. Enrollment 
Subject enrollment occurs at the time of surgery. Every subject that receives the study device will be considered 
enrolled in the study.  If a subject has provided consent and completed screening, and for any reason does not 
receive study device, the subject will not be considered enrolled in the study. 
Therefore pre-operative CRFs will not be submitted to the Sponsor until the subject is actually enrolled 
(treated with study device) in the study.  
 
7.3. Conditions for Study Termination 
Reasons for termination of study participation are described below.  
 
A. Screening Failure 
Subjects who have provided informed consent but did not receive the study device are considered screen 
failures. The reason for screening failure must be captured on the Screening and Enrollment Log maintained in 
the Investigator Master File. No CRFs will be collected. 
 
B. Voluntary Withdrawal 
Study participation is voluntary and subjects may withdraw at any point during the study without giving their 
reason for doing so. CRFs are collected until time point of withdrawal. 
 
C. Subject Termination by Investigator 
The Investigator should withdraw subjects from the study in case the study device cannot be implanted during 
surgery for any reason. 
Subjects that do not receive the study device are not considered as enrolled and will be documented on the 
Screening and Enrollment Log.   
 
D. Study Termination 
The Sponsor may choose to discontinue the study at any time. In which case, the subjects will be followed up 
according to the standard practice of the site. 
 
E. Study Site Discontinuation 
A specific study site in this multicenter study may also warrant termination under the following conditions: 
• 
non-compliance to Good Clinical Practice (GCP) or protocol 
• 
failure to enroll subjects 

 
 
 
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• 
inaccurate or incomplete data 
• 
unsafe or unethical practices 
• 
safety or performance considerations 
 
In this case, enrolled subjects will be followed up according to the standard practice of the site. 
 
8. SAFETY REPORTING  
Adverse events and device deficiencies, noted by study staff and reported by the subject, and occurring from the 
time of study device implantation through to study completion should be recorded on the appropriate CRFs and 
reported as below.  
 
8.1. Definitions for safety reporting 
A. Adverse Event (AE) 
An AE is 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 [8]. 
This definition includes: 
• 
events related to the investigational medical device or the comparator 
• 
events related to the procedures involved 
• 
a worsening of any conditions previously recorded as part of the medical history assessment 
For users or other persons, this definition is restricted to events related to investigational medical devices. 
 
B. Serious Adverse Event (SAE) 
A SAE is an adverse event that [8]: 
• 
led to death, 
• 
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 
• 
led to foetal distress, foetal death or a congenital abnormality or birth defect 
 
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. 
 
C. Adverse Device Effect (ADE) 
An ADE is an adverse event related to the use of an investigational medical device [8]. 
 
This definition includes: 
• 
adverse events resulting from insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device 
• 
any event resulting from use error or from intentional misuse of the investigational medical device. 

 
 
 
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D. Serious Adverse Device Effect (SADE) 
An SADE is an adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event [8]. 
 
E. Unanticipated Serious Adverse Device Effect (USADE) 
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 or the clinical investigation plan [8, 9]. 
 
F. 
Device Deficiency 
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, durability, reliability, 
safety or performance. Device deficiencies include malfunctions, use errors, and inadequate labelling.  
 
For the purpose of this study, device deficiencies should be reported when they concern any component of the 
study device as well as its packaging and tools that need to be used during implantation according to the 
Instructions for Use. 
 
8.2. Safety: Investigator’s Responsibilities 
Investigators shall record AEs and DDs, together with an assessment, in the subject’s source data. Following, 
Investigators are responsible for documenting AEs and DDs on the appropriate CRF and submitting them to the 
Sponsor according to the timelines described below.  
AEs must be recorded in standard English medical terminology.  
 
Unresolved AEs should be followed by the Investigator until the events are resolved, the subject is lost to follow-
up or through to the end of the study, whichever timing occurs first. Unresolved AEs at the end of the subject’s 
participation will be monitored by the Investigator as part of the site’s normal standard of care. 
 
The Investigator will categorize AEs as mild, moderate or severe based on the following definitions: 
• 
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 wellbeing. 
• 
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 wellbeing and may require medical intervention 
and/or close follow-up. 
• 
Severe:  the adverse event interferes considerably 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 wellbeing.  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.   
The Investigator is responsible for describing the relationship of the AE to the study device/procedure based on 
the following definitions: 
• 
Unrelated: the event is clearly not related to the study device or procedure 
• 
Possible: the event may or may not be related to the study device or procedure.  A relationship cannot 
be ruled out. 
• 
Definite: the event is clearly related to the study device or procedure. 
 
 
 

 
 
 
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8.3. Timelines for Submission of Safety Information: 
The timelines begin when the Investigator becomes aware of the event. 
The Investigator will report to the Sponsor: 
• 
As soon as possible, but no greater than  24 hours  upon becoming aware of the event: 
o 
SAEs 
o 
SADEs 
o 
USADEs  
o 
DDs that could have led to a SADE: 
 
if suitable action had not been taken 
 
if intervention had not been made, or 
 
if circumstances had been less fortunate 
o 
Re-operation at the study site. Sponsor will provide an explant retrieval kit on becoming aware 
of a revision and ask the Investigator to return any revised components for retrieval analysis. 
Investigators may also be asked to supply the Sponsor, upon Sponsor’s request, with any additional information 
related to the safety reporting of a particular event. 
 
The PI will be responsible for reporting to the EC of the study site and to the regulatory authorities, SAEs, SADEs 
and DDs that could have led to a SADE, as required by the national regulations.  
 
8.4. Safety reporting: Sponsor’s Responsibilities 
Sponsor will provide progress reports on safety events to the Investigator to report to the EC as required.   
In the case of multicenter studies, Sponsor will inform all Investigators in writing of all SAEs that were reported 
by all sites throughout the clinical investigation and based on perceived risk. 
The Sponsor will also, in case of SADEs and DDs that could have led to SADEs, determine whether the risk 
analysis needs to be updated and assess whether corrective or preventive action is required. 
 
 
 
 
 

 
 
 
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9. STATISTICAL PROCEDURES  
9.1. Hypothesis and Sample size calculation 
The following hypotheses will be tested: 
 
H0:  
The null hypothesis is that there is no mean difference between the position of the last trial rasp and 
the final implant position of the SL-PLUS™ MIA Ti/AH femoral hip stem. 
H1:  
The alternative hypothesis is that there is a mean difference between the position of the last trial rasp 
and the final implant position of the SL-PLUS™ MIA Ti/AH femoral hip stem. 
 
The study hypothesis can be written as: 
H0: µ=0  vs.  H1: µ
≠0
 
 
In 2007, a non-published cadaver test was performed to measure the difference D between the position of the 
last trial rasp and the implant position of the SL-PLUS™ MIA Ti/AH femoral hip stem. A total of 4 femoral hip 
stems were implanted into the cadaveric femur. The range of the measured difference was found to be 
between 0mm and 6mm. However, it is most likely that the maximum difference will be greater 6mm when 
more cases are studied. To compensate for the small number of evaluated cases, the anticipated variation in D 
will be extended to 10mm with an estimated standard deviation of 2.5mm. A correlation ρ between the 
distances x1 and x2 is certainly positive but it is unknown how strong the correlation is. The standard deviation 
sd of the difference D has the following relationship with the standard deviations sd1 and sd2 for distances x1 
and x2: 
sd2 = sd1
2 + sd2
2 −2ρsd1sd2 
 
Since ρ>0 and assuming that ρ=0 will lead to a larger sd and therefore a larger sample size. If assumed that 
sd1=sd2, then sd2=2sd1
2. So assuming sd1 and sd2 being equal, the sd will also lead to a larger sample size. 
Therefore, assuming that the correlation is zero and allowing for both standard deviations sd1 and sd2 to be 
2.5mm is a conservative approach for computing sample size. 
According to orthopaedic surgeons, the maximum difference between the position of the rasp and implant 
without clinical significance is considered to be 2mm. The standard deviations of sd1 and sd2 are estimated as 
approximately 2.5mm estimated based on the assumptions above and data for the range of difference.. 
The sample size calculation is based on a two-sided test. The significance level and power of the study are 
chosen to be 0.05 and 0.90; the minimum mean difference Δ is identified as 2 mm; the standard deviations sd1 
and sd2 are 2.5mm; the correlation between x1 and x2 is set to 0. The following formula can be used to 
calculate the sample size: 
 
N ≥2(TN−1,α/2 + TN−1,β)2sd2
∆2
 
 
The SAS POWER procedure is used to compute the sample size and at least 35 subjects are needed for the 
study. 
 
9.2. Statistical Analysis 
All subjects who meet the study inclusion and exclusion criteria will be included in the statistical analysis. 
Statistical analyses will be conducted for demographics, pre-operative information, surgical information and 
safety data. Demographics will include, but not limited to, gender, age, weight, height, BMI. Pre-operative 
information and surgical information will include any data collected as defined in this protocol.  Safety data will 

 
 
 
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include adverse events, serious adverse event, adverse device effect, serious adverse device effect, 
unanticipated serious adverse device effect, and device deficiency.  
Descriptive statistics for continuous variables will include mean, median, minimum, maximum, standard 
deviation, and 95% confidence interval, if appropriate. Descriptive statistics for discrete variables will include 
count and percentage.  
Subgroup analyses will be provided if they are necessary. The following sections define the details of primary 
endpoint and secondary endpoints analyses. 
 
9.2.1. Primary Endpoint Analysis 
If the difference between x1 and x2 measured from fluoroscopic images approximately follows a normal 
distribution, then a two-sided paired T test will used to test the mean. The test statistic is a t-score defined by the 
following equation: 
 
T=𝐷/(sd/√𝑁) 
 
where  
 
𝐷=𝑁−1 ∑
(𝑥𝑖1 −𝑥𝑖2)
𝑁
𝑖=1
 
sd= ට∑
(𝑥𝑖−𝐷)2/(𝑁−1)
𝑁
𝑖=1
 
𝑥𝑖= 𝑥𝑖1 −𝑥𝑖2, i=1, … N.   
 
The SAS TTEST procedure will be used to perform the paired T test.  If the difference does not follow a normal 
distribution, then the signed rank test will be used to test the hypothesis. The SAS UNIVARIATE procedure will be 
used to perform the signed ranked test. 
 
The null hypothesis will be or not be rejected based on corresponding observed p value from the test above. An 
alpha value of 0.05 will be used in the hypothesis testing. 
 
9.2.2. Secondary Endpoint Analysis 
Descriptive analyses will be presented for the secondary endpoints of leg length discrepancy and intraoperative 
complications.  
 
9.3. Missing Data  
The primary endpoint is an intraoperative measurement so there is no expectation for missing data due to lack of 
follow up. However, the primary endpoint could be missing due to other issues such as unreadable images. 
Allowing for 12% missing data, a total sample size of 40 cases is needed in the study. 
 
 
 
 

 
 
 
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10. ETHICAL CONSIDERATIONS 
10.1. Ethical Approval 
In accordance with the Declaration of Helsinki and local regulations of the participating countries, sites must gain 
written EC approval prior to enrolling research participants in the study.  
 
10.2. Protocol Amendments 
Neither the Investigator nor the Sponsor will modify this protocol without mutual agreement. After agreement to 
initiate the modification - in the form of a protocol amendment - the Investigator agrees not to implement this 
modification until instructed to do so by the Sponsor. It will be necessary to obtain EC approval prior to 
implementation of any change in the protocol that may affect the scientific soundness or the rights, safety, or 
welfare of the subjects involved. Notification shall be submitted to the EC of the study site by the Investigator.  
 
10.3. Informed Consent 
All study subjects must sign an EC approved ICF according to 2011:ISO14155 guidelines, GCP guidelines and all 
applicable national regulations. Potential subjects must be informed as to the purpose of the study and the 
potential risks and benefits known or that can be reasonably predicted or expected as described in the written 
consent form. The subject shall have sufficient opportunity to consider participation in the study; a subject 
cannot be led to believe that they are waiving their rights as a subject or the liability of the Sponsor or 
Investigator. Subjects are then invited to sign and date the consent form, indicating their consent for 
enrollment. The Investigator will retain the original copy of the signed consent form in the study files. A 
duplicate copy shall be provided to the subject. 
 
10.4. Risk – Benefit Analysis 
A. Study Related Risks 
Possible risks that may occur as a result of study procedures are: 
• 
This study involves the use of x-ray and fluoroscopic evaluation. X-ray exposure is cumulative over a lifetime 
and total exposure should be kept to a minimum. However, if the x-ray exposure when participating in the 
study is equivalent to the exposure the subject would receive if they chose not to participate in the study, 
there is no additional risk associated with this study. 
• 
As a result of participating in the study there could be a risk of loss of protected subject information 
confidentiality. All applicable confidentiality standards and data protection and privacy laws will be followed 
by the Sponsor to ensure that data collected is handled in confidence. Data will be coded and handled only 
by appropriately qualified and authorized personnel. 
Risks related to the general surgical procedures and exposure to x-ray for preoperative planning are not 
considered here because these risks are equivalent whether the subject participates in the study or not. 
 
B. Study Related Benefits 
Because the surgery and all the follow-up visits are the same as when the subject would not participate in this 
study, there are no additional medical benefits associated by participating in this study. The information gained 
from this study may help to improve the existing instruments used for the implantation of the SL-PLUS™ MIA Ti/HA 
femoral hip stem and in consequence improve the treatment of patients that need to undergo THA. 
 
 

 
 
 
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11. MONITORING PROCEDURES 
11.1. Source Documentation 
Investigators are responsible for obtaining and maintaining complete subject health information in the medical 
record for each subject (source documents). Examples of source documents are: hospital records, clinic and 
office charts, memoranda, dispensing records, subject questionnaires, clinic evaluation transcriptions, operative 
notes, x-rays, radiology reports, blood collection reports and shipment records, and research subject files.   
CRFs may be used as source documents if they represent data collected for the study and are the location that 
data is initially recorded. 
 
As a minimum entry in the medical records, the PI shall ensure that clinical records are clearly marked to indicate 
that the subject is enrolled in a particular clinical study and if they completed per protocol or discontinued early 
and the reason. 
 
11.2. Direct Access 
This study may be monitored by the Sponsor or a qualified person designated by the Sponsor. This qualified 
person could be an employee of the Sponsor or of a contract research organization (Sponsor’s agent).  
 
The Investigator will provide Sponsor, Sponsor’s agents, EC and regulatory agencies with direct access to all 
source data/documents to permit study-related monitoring, audits, EC review, and regulatory inspections. 
 
11.3. Site Qualification Visit (SQV) 
A SQV may be performed by the Sponsor prior to the execution of a clinical agreement to ensure that all 
Investigators have the appropriate training, staff, facilities and resources to adequately conduct the study. 
 
11.4. Prior to Study Initiation 
The Investigator must ensure the activities below are completed prior to the initiation of the study and provide 
supporting documentation to the Sponsor: 
 
• 
Clinical Study Agreement: must be fully executed with the site and the Sponsor and any other appropriate 
party. 
• 
Documentation of Qualifications: a current, signed and dated Curriculum Vitae (CV) for Investigator and 
for all key members of Investigator study site team listed on the Delegation of Authority Log must be 
submitted to the Sponsor prior to the study and updated as applicable to staff changes and confirmed at 
close out visit. 
• 
Conflict of Interest: all participating Investigators are required by ISO 14155 to provide details of conflict of 
interest (including financial, if applicable) according to local regulations.  This information must be updated 
promptly by the Investigator and submitted to the Sponsor if any changes occur through the duration of the 
study and for one year following completion of the study. 
 
11.5. Site Initiation Visit (SIV) 
A SIV to provide training on the specifics of the study, site obligations and expectations of study conduct will be 
performed by the Sponsor following execution of the Clinical Study Agreement and documented EC approval.  
 
 

 
 
 
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11.6. Interim Monitoring Visits (IMVs) 
Due to the short length of the study no IMVs will be performed. 
 
11.7. Sponsor Audits and Regulatory Inspection 
Quality assurance auditors, whether an employee of the Sponsor or its designee, may evaluate study conduct at 
the study sites. These parties must have access to any and all study reports and source documentation, 
regardless of location and format.  
 
11.8. Close Out Visit (COV) 
A study COV will be performed by the Sponsor or designee to retrieve and account for all remaining clinical data 
and to resolve outstanding queries.  During study close-out, the monitor will review the Investigator Master File to 
ensure required documents and records are on file, confirm the disposition of any other ancillary items used for 
the study, and review regulatory requirements regarding records retention and EC reporting requirements.  
During the COV the monitor will further: 
• 
verify the informed consent process  
• 
perform source data verification   
• 
verify that source documentation is complete and available 
• 
ensure compliance with the protocol 
 
11.9. Documentation of Site Visits  
Activities associated with a monitoring visit (SQV, SIV, COV) will be documented by the monitor. This includes: 
• 
monitor visit log on site 
• 
a Follow-Up letter to the Investigator following each visit summarizing the visit and detailing 
any site deficiencies and action items to clarify or address issues noted 
 
11.10. 
Data Handling and Record Keeping Requirements 
CRFs will be supplied by the Sponsor. Subjects will be identified by a study number and subject identification 
code. Only the Investigator site will have the key to identify individual subjects.  
The Investigator is responsible for the timely and accurate completion of CRFs. All documents related to the study 
must be securely archived at the study site or in a central archive.  
Data required according to this protocol are to be recorded on the CRFs at the time of the scheduled visits. Once 
a subject is enrolled, completed CRFs should be sent to the Sponsor, either by fax or by e-mail, as soon as 
possible, and no later than 10 working days upon completion of the CRFs. 
 
11.11. Data Recording and Record Retention 
Clinical research records shall be stored in a manner that ensures privacy, confidentiality, security and 
accessibility of the records both during and after the conduct of the study. The Investigator/Institution will take 
measures to prevent accidental or premature destruction of those documents. The Investigator must retain 
essential study documents for at least 2 years after the date the study is terminated or completed. If the 
Investigator needs to dispose of the documents, the Sponsor should be contacted for approval prior to disposal 
or destruction. For discontinued product, the essential documents will be retained until at least 2 years have 
elapsed since the formal discontinuation (via notification of the FDA or other regulatory agency) of clinical 
development of the investigational product. The Investigator will retain these documents for a longer period if 
required by the applicable local laws. 

 
 
 
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If the responsible Investigator retires, relocates, or withdraws from responsibility of keeping the study records, 
custody must be transferred to a person who will accept the responsibility.  The Sponsor must be notified in 
writing of the name and address of the new custodian. Under no circumstance shall the Investigator relocate or 
dispose of any study documents before having obtained written approval from the Sponsor. 
 
12. DEVIATIONS FROM PROTOCOL 
A protocol deviation is an instance of failure, intentionally or unintentionally, to follow the requirements of the 
protocol. Protocol deviations include but are not limited to: deviations from inclusion/exclusion criteria, endpoint 
variable criteria, study visits outside the window, and GCP guidelines. 
 
12.1. Protocol Deviation Reporting Requirements 
Deviations must be reported to the Sponsor through the specially designed Protocol Deviation Log as soon as 
reasonably possible.  
 
When protocol deviations affect the scientific soundness of the study, or the rights, safety or welfare of the study 
subjects, the Investigator must also report protocol deviations to the EC of the study site. It is the responsibility of 
the PI to inform the EC of the incident, per local requirements. The local EC should be consulted on protocol 
deviation reporting requirements.   
 
Investigators and all study staff (staff at site and at Sponsor) are responsible for ensuring adherence to study 
protocol. During the monitoring visits, the Sponsor representative will review all deviations with the Investigator. If 
a deviation is discovered outside of a monitoring visit, it should be evaluated via phone, email or letter. 
Appropriate measures to address the occurrence, additional monitoring visits, or audit of the study should be 
taken, which may include defining and implementing a Corrective and Preventive Action (CAPA).  
 
13. PUBLICATION POLICY 
13.1.  Multicenter Publication 
The Sponsor may invite the Investigator to participate in a multicenter publication of the study results, in which 
case it will be ensured that the documents submitted for publication comply with the publisher’s requirements for 
authors and contributors. If the publisher has no such requirements, it will be ensured that the publication meets 
the authorship and contributorship requirements as stated in the current Smith & Nephew Global Policy and 
Procedure relating Scientific Disclosures. Also, the Sponsor will select a publisher based on mutual agreement 
with the Investigators, who are invited to participate in the publication. 
 
13.2. Investigator Publication 
The Investigator may publish his/her own data subject to the following restrictions: 
- 
the multicenter manuscript must be published prior to Investigators publishing their own data; 
- 
the manuscript shall be submitted to the Sponsor for review prior to submitting the manuscript for 
publication; 
- 
the manuscript must reference the study multicenter manuscript. 
 
 
 

 
 
 
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13.3. Authorship 
Unless otherwise required by the journal of publication or the forum in which a presentation is made, authorship 
will comply with ICMJE current Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing 
and Editing for Biomedical Publication.  ICMJE recommends that authorship be based on the following criteria:  
 
- 
Substantial contributions to the conception or design of the work; or the acquisition, analysis, or 
interpretation of data for the work; and  
- 
Drafting the work or revising it critically for important intellectual content; and 
- 
Final approval of the version to be published; and 
- 
Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy 
or integrity of any part of the work are appropriately investigated and resolved.  
- 
In addition to being accountable for the parts of the work he or she has done, an author should be able to 
identify which co-authors are responsible for specific other parts of the work. In addition, authors should 
have confidence in the integrity of the contributions of their co-authors.  
Subject to a publisher’s copyright, Site and/or Investigator will own the copyright on publications and other 
copyrightable material produced as a result of the Study. 
 
 
 

 
 
 
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BIBLIOGRAPHY 
1. 
Hart, J.A., Joint replacement surgery. Med J Aust, 2004. 180(5 Suppl): p. S27-30. 
2. 
Konyves, A. and Bannister, G.C., The importance of leg length discrepancy after total hip arthroplasty. J 
Bone Joint Surg Br, 2005. 87(2): p. 155-7. 
3. 
Barink, M., et al., How close does an uncemented hip stem match the final rasp position? Acta Orthop 
Belg, 2004. 70(6): p. 534-9. 
4. 
Hozack, W.J., Mesa, J.J., and Rothman, R.H., Head-neck modularity for total hip arthroplasty. Is it 
necessary? J Arthroplasty, 1996. 11(4): p. 397-9. 
5. 
Surgical Technique SL-PLUS MIA Cementless Fenoral Hip System, S.N.O. AG, Editor. 2015. 
6. 
Dorr, L.D., et al., Structural and cellular assessment of bone quality of proximal femur. Bone, 1993. 14(3): 
p. 231-42. 
7. 
Sabharwal, S. and Kumar, A., Methods for assessing leg length discrepancy. Clin Orthop Relat Res, 
2008. 466(12): p. 2910-22. 
8. 
Clinical investigation of medical devices for human subjects - Good clinical practice (ISO 14155:2011), in 
SN EN ISO 14155. 
9. 
Code of Federal Regulations Title 21. 2014. 21CFR812.