A Randomized, Blinded, Cross-over Trial to Evaluate the Safety, Functional Mobility and Satisfaction of the Microprocessor Controlled Prosthetic Knee Component C-Leg 4 in Transfemoral Amputees
Phase: NA
Conditions: Lower Limb Amputation Above Knee (Injury)
Sponsor: Otto Bock Healthcare Products GmbH

 
 
 
 
 
 
 
 
Post-market Study Protocol 
A randomized, blinded, cross-over trial to evaluate the safety, functional mobility and 
satisfaction of the microprocessor controlled prosthetic knee component C-Leg4 in 
transfemoral amputees 
C-Leg 3 and C-Leg 4 Study in Transfemoral Amputees 
Protocol ID:  PD-PS00120010A-001 
ClinicalTrials.gov ID:  NCT02765035 

Post-market study ,,C-Leg" 
Version 1.0, 15.12.2015 
ottobock. 
,, A randomized, blinded, cross-over trial to evaluate the safe-
ty, functional mobility and satisfaction of the microprocessor 
controlled prosthetic knee component C-Leg4 in transfemoral 
Created by 
Approved 
Vers. No. 
1.0 
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amputees" 
a post-market study 
Document number 
PD-PSO0 12001OA-001 
CONFIDENTIAL DOCUMENT 
Name/Function 
Datum 
Signature 
Dr. Ivana Sreckovic 
lvaLW 
' 
I 
I!_-- 1J w,!{ 
JYet uo <--) 'c. 
Clinical Project Manager 
I 
/ 
Name/Function 
Datum 
"'"'~ () 
Dr. Andreas Hahn 
Corporate Vice President 
2.A . A?. . 2.v tr 
Description 
Valid from 
Creation of the clinical trial protocol 
Signed release 

Post-market study ,,C-Leg" 
ottobock. 
Version 1.0, 15.12.2015 
Principal Investigator: 
Prim. Priv.Doz. Dr. Stephan Domayer, PhD 
Co-Investigator: 
Sponsor: 
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Head of Orthopedic Rehabilitation Center SKA Zicksee 
Otto Pohanka Platz 
7161 St.Andra am Zicksee 
Austria 
Tel: +43 (0)2176/2325 - 123 
Fax: +43 (0)2176/2325 130 
stephan.domayer@skazicksee.at 
Dr. Carlotte Kiekens 
Head of Physical Medicine and Rehabilitation Clinic 
UZ Leuven, Pellenberg Campus 
Weligerveld 1 
B - 3212 Pellenberg 
Belgium 
Tel +32 16 33 87 00 
Fax +32 16 33 87 03 
carlotte.kiekens@uzleuven.be 
Dr. Andreas Hahn 
Otto Bock Healthcare GmbH 
BrehmstraBe 16, 
1110 Vienna 
Austria 
Tel.: +43-1-526-5812 - 635 
Fax: +43-1-526 58 12 - 291 
Mobile: +43-664-1468 252 
andreas.hahn@ottobock.com 

Post-market study ,,C-Leg" 
Version 1.0, 15.12.2015 
Signature sheet 
Sponsor 
Dr. Andreas Hahn 
Clinical Research and Services 
Corporate Vice President 
Otto Bock Healthcare Products GmbH 
c:. J /p__?p(( 
Date, Place and signature 
Principal Investigator 
Prim. Priv.Doz. Dr. Stephan Domayer, PhD 
Head of Orthopedic Rehabilitation Center 
SKA Zicksee 
~l.A~ 1 
Z..f. ,r1. 
Date, Place and s 1i;1101ure 
Co-investigator 
3/28 
Dr. Carlotte Kiekens 
Head of Physical Medicine and Rehabilitation Clinic 
UZ Leuven 
Date, Place and signature 
ottobock. 

Post-market study ,,C-Leg" 
Version 1.0, 15.12.2015 
Table of Contents 
1 
Overview 
2 
List of Abbreviations 
3 
Background 
4 
Device information 
5 
Study objectives 
6 
Study design 
7 
Patient population 
8 
Statistics 
9 
Study sites and patient recruitment 
10 
Randomization 
11 
Risk benefit analysis 
12 
Management of adverse events 
11 
Monitoring of clinical trial 
12 
Study Discontinuation 
13 
Ethical considerations 
14 
Disclosure of data and publication policy 
15 
References 
16 
Appendix 
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5 
6 
7 
8 
9 
9 
16 
18 
19 
20 
20 
21 
22 
24 
24 
25 
26 
28 

Post-market study ,,C-Leg" 
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1 
Overview 
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During the last two decades many MPK appeared on the market. Despite that additional func-
tionality and safety of MPK over mechanical knee joints are assumed, not for every MPK addi-
tional benefit was proven. 
The newly developed C-Leg4 aims to provide improved standing function while in the same 
time offering technology of knee's previous version (C-Leg-3). Since added functional benefit 
of a knee joint cannot be anticipated just due to the fact that the knee is controlled by the mi-
croprocessor, the aim of this post-market study is to evaluate the safety, functional mobility 
and satisfaction of the microprocessor controlled prosthetic knee components C-Leg3 and C-
Leg4 in comparison with mechanical knee joints. Additional goal of this post marketing 
study is to improve the methodological quality of research conducted in the field. 

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2 
List of Abbreviations 
Abbreviation 
6MGT 
l0mGT 
ABC 
ABIS 
AE 
AR 
CRF 
eCRF 
FSST 
HAI 
ITT 
MPKs 
MFCL 
NMPKs 
PLUS-M 
SAE 
SAI 
SAR 
pp 
UAR 
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Definition 
6 Minute Gait Test 
10 Meter Gait Test 
Activities-specific Balance Confidence 
Amputee Body Image Scale 
Adverse Event 
Adverse Reaction 
Case Report Form 
electronic Case Report Form 
Four Step Square Test 
Hill Assessment Index 
Intention-To-treat (ITT) 
Microprocessor Controlled Knees 
Medicare Functional Classification Level 
Non-Microprocessor Controlled Knees 
Prosthetic Limb Users Survey of Mobility 
Serious Adverse Event 
Stairs Assessment Index 
Serious adverse reaction 
Per-Protocol 
Unexpected adverse reaction 

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3 
Background 
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For the individual with lower limb amputation, it is crucial to select an appropriate prosthetic 
device which can restore much of the ambulatory function that has been lost and has an impact 
on patient's safety as it relates to stumbles, falls and balance. 
Several studies investigated changes in ambulation when lower limb amputees walked on C-Leg 
and non-microprocessor controlled knees (NMPKs). The improvements of self-selected walking 
speed ranged from 7 .3o/o up to 15o/o (average difference 0. lm/s) (Orendurff et al 2006, Segal et al 
2006, Kahle et al 2008), while the fastest possible walking speed was improved up to 17o/o (aver-
age difference 0.2m/s) (Kahle et al 2008) with C-Leg compared to NMPKs. Although the design of 
used outcome measures varied throughout the trials as well as the target population, each study 
reported an increase in walking speed when ambulating with a C-Leg compared to NMPKs. These 
could be possible explanations why the reported self-selected walking speed of transfemoral am-
putees fitted with C-Leg ranged from 0.98m/s up to 1.39 m/s (Kahle et al. 2008, Orendurff et al 
2006, Segal et al 2006, Bellman et al 2010), while reported values for fastest walking speed 
ranged from 1.19m/s up to 1.66 m/s (Orendurff et al 2006, Bellman et al 2010). Despite this vari-
ety, walking speed is valuable outcome. Walking speed has been shown to be associated with 
survival among older adults and has been shown to reflect health and functional status (Abellan 
et al., 2009). Gait speed has been recommended as a potentially useful clinical indicator of well-
being among the older adults (Hall et al., 2006). Improvement of 0.lm/s in comfortable gait 
speed over a 1-year period strongly predicts survival through the subsequent 8 years, with a 58o/o 
reduction in relative risk and a 17. 7o/o reduction in absolute risk of death (Hardy et al., 2007). 
Additionally, an improvement of 0. lm/s in gait speed predicts higher ambulatory category (Perry 
et al., 1995) and cost reduction (Purser et al., 2005). 
Safety and confidence in the prosthesis play an important role in the amputee, s life. Fall always 
represents a potential harm for health and trust in prosthesis. The fear of falling is one of the ma-
jor factors for decreased activity, mobility, and quality of life. Miller et al. 2001 reported that 
among community-living persons with lower extremity amputation, 52o/o had fallen in the past 12 
months, 49o/o had a fear of falling, and 65o/o had low balance confidence scores. When using C-
Leg compared to NMPKs, stumbling was reduced by 25o/o, semi-controlled falls by 17o/o and fall-
ing by l0o/o (Hafner et al 2007). Even a larger decrease with C-Leg compared to NMPKs, namely 
stumbles by 59o/o and falls by 64o/o, was reported by Kahle et al (2008). Limited community am-
bulators profit from a transition from a NMPK to C-Leg with a decrease in falls by even 80o/o. K3 
subjects reduced the frequency of stumbles by 31 o/o when using C-Leg (Hafner et al 2009). Fur-
thermore, the most recent study reported that falls were reduced by 33o/o with C-Leg compared to 
NMPKs (Highsmith et al 2014). Similar observations are further confirmed in other studies 
(Drerup et al 2008, Wong et al 2012). Finally a case report showed that Berg Balance Scale score 
and Activities-specific Balance Confidence (ABC) Scale improved immediately with C-Leg after 
only one hour of training compared to a NPCK (Wong et al 2012). 
Performance in descending stairs and ramps is improved with C-Leg compared to NMPK (Hafner 
et al 2007, Kahle et al 2008, Hafner & Smith 2009). Furthermore, subjects improved their perfor-
mance in activities of daily living (Theeven et al 2011) as well as overall quality of life (Hafner et 
al 2007, Kahle et al 2008, Hafner & Smith 2009) with C-Leg compared to NMPKs. This indicated 
that the use of MPK allows for amputees to participate in a wider range of activities of daily living 
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and thereby providing a higher participation in their community and hence society. Therefore it is 
not surprising that a high majority of subjects prefer MPK compared to NMPK. 
Evidence collected during the last two decades suggests that in comparison to mechanical knee 
joints C-Leg improves the user's safety, ability to walk faster, to negotiate stairs, hills and partici-
pate in a wider range of activities of daily living. In the same period of time many MPK appeared 
on the market. Despite this additional functionality and safety of MPK over mechanical knee 
joints are assumed, not for every MPK additional benefit was proven (Prinsen et al., 2014, Hafner 
2015). The newly developed C-Leg4 aims to provide improved standing function while in the 
same time offering technology of the knee's previous version (C-Leg-3). Since added functional 
benefit of a knee joint cannot be anticipated just due to the fact that the knee is controlled by the 
microprocessor, the aim of this post-market study is to confirm that the microprocessor controlled 
prosthetic knee components (C-Leg3 and C-Leg4) in comparison to mechanical knee joints can 
bring additional benefit to the user primarily on level walking and secondary on safety, stairs and 
hills mobility, activities of daily living, satisfaction and preference. Second study hypothesis is 
that C-Leg4 can improve primarily users ability to walk on even terrain, and secondly on stairs, 
hills, as well as to increase safety, satisfaction and participation in activities in daily living. 
It needs to be stated that additional goal of this study is to improve methodological quality of the 
research conducted with prosthetic knee joints. Recent published data are generally rated as 
providing moderate to low levels of evidence because of structural weakness of the study designs. 
These weaknesses are mostly caused by low statistical power due to the small sample number and 
high dropout rates, a lack of blinding, and precise measures with no estimate of minimal detecta-
ble changes(MCD) (Orendurff et al., 2013). At least two areas of methodological improvement 
will be addressed in presented research: 1) blinding of the users, assessors and statistician, and 
2) larger numbers of participants will be enrolled. 
4 
Device information 
Both C-Leg3 and C-Leg4 are driven by a microprocessor-controlled hydraulic unit that dynamical-
ly adapts the system to all gait speeds in real time. It has a microprocessor controlled swing- and 
stance control. Customizable software settings and internal sensors enable an intelligent control 
of the microprocessor-controlled knees - the system always recognizes the specific phase of gait 
performed by the user. The microprocessor ensures that the damping of the hydraulic unit is al-
ways adjusted to the specific situation, from highest safety during the heel strike to the easy 
changeover to swing. This is always done in real time - irrespective of whether the knee user is 
walking fast or slowly, or with long or short steps. As a result, the user may move freely and easily 
whatever the surface - be it on level or uneven ground or stairs or walking on inclines. 
With C-Leg3, the swing phase is triggered when following requirements are fulfilled: the knee 
angle sensor measures that the knee prosthesis is in a fully extended position and there is no flex-
ion movement released. Two strain gauge strips measure the load on the foot. A defined load 
threshold has to be exceeded that swing phase is released. 
C-Leg4 requires following conditions to release to swing phase: Equivalent to C-Leg3 a knee angle 
sensor measures that the knee is in full extension, and additionally, a disc spring measures very 
precisely hyperextension of the knee which is a criterion for swing phase release. The knee angle 
sensor and the disc spring function together as a knee moment sensor, which enables release of 
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the swing phase independent form a toe load. Together in combination with the position sensor 
which assures correct positioning of the prosthesis, the movement of the foot can be calculated. 
This leads to the easier transition from stance to the swing phase. Furthermore, standing with the 
flexed knee is now easier with C-Leg4. 
S 
Study objectives 
As stated above, for the lower limb prosthesis it is crucial to restore much of the ambulatory func-
tion that has been lost. Therefore the primacy objective is to evaluate the effect of the micropro-
cessor controlled knees (C-Leg3 and C-Leg4) on the level walking in comparison to conventional 
mechanical knees. 
The secondacy objectives are to evaluate the effect of the microprocessor controlled knees (C-
Leg3 and C-Leg4) on safety, self-reported balance confidence, number of stumbles and falls, 
stairs and hills mobility, activities of daily living, satisfaction and preference in comparison with 
a non-microprocessor controlled knee. 
6 
Study design 
6.1 Experimental plan 
A randomized crossover design will be used in this post marketing study. Amputees currently 
wearing mechanical prosthesis and fulfilling inclusion/exclusion criteria will be enrolled in the 
study. After recruiting, functional level, demographic, anthropometric, clinical and "O" baseline 
data will be collected. The certified prosthetist will evaluate the participants' socket and the foot. 
If the socket are inadequate (e.g participant has subjective problems, the fitting of the socket is 
unsatisfactory or insufficient for a MPK fitting), the prosthetist will create and fit a new socket, for 
others copy of the socket will be created. All participants will be fitted with Otto Bock carbon 
spring feet, where Triton foot will be the first choice to the highest possible extent. Participants 
will also receive a foam cosmetics which will be used during the entire study. Four weeks of ac-
climation period to a new socket and foot will be given. The physical therapy will be provided to 
ensure the best output of mechanical knee joints. The physical therapy with NMPK will have two 
mandatory sessions plus one optional one if the participant demands it. The participant will re-
ceive training from the study physical therapist on the functions of the NMPK knee for walking on 
level ground, inclines, declines, up & down the stairs, and uneven ground. Performance will be 
assessed before (1st Baseline measurement) and 2 weeks after physically therapy sessions (2nd 
Baseline measurement) to check if the administered therapy had any influence on the outcome. 
The second data recording will be used as the official baseline measurement ("A phase - meas-
urement with mechanical knee joint"). 
Afterwards the participants will be randomly assigned to be fitted either with C-Leg4 or C-Leg3. 
The randomization procedure will be concealed and assigned off-site. The fitting of Otto Bock C-
Leg4 or C-Leg3 will be performed by a certified prosthetist and physical therapy will be provided. 
The physical therapy will include 5 rehabilitation sessions plus one optional to ensure that partic-
ipants are properly using the microprocessor controlled knee. After the therapy participants will 
be offered an acclimation period that will last up to 90 days prior to undergoing testing with the 
MPK ("B phase - measurement with C-Leg4/C-Leg3"). Hafner et al., 2007 suggested the criteria 
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that MPK user needs to fulfil to be fully acclimatized to MPK. The users are allowed to accommo-
date until they (1) show stable alignment in the test prosthesis (checked and evaluated by certi-
fied prosthetist), (2) require no additional changes to the C-Leg software settings (checked and 
evaluated by certified prosthetist), and (3) verbally acknowledge and physically demonstrate that 
they are able to perform "proficient-use" tasks (independently ambulate on level ground, de-
clines, inclines, stairs, and uneven terrain) that each subject previously showed in the mechanical 
control prosthesis. Once all three criteria are fulfilled, they are asked to wear the microprocessor 
control prosthesis regularly for a period of 1 month. The number of falls will be measured and 
documented by the user during the last month the device is used. 
After the first follow-up data collection, the participants will cross over to the second MPK. The 
participants who were fitted with C-Leg4 will cross over to C-Leg3 and vice versa. The physical 
therapy (2 mandatory + one optional session) will be offered to facilitate the transition to another 
knee joint. The same criteria will be used to estimate acclimatization with the second MPK joint, 
which will be used for the period of 30 days, followed by the data collection ("C phase - meas-
urement with C-Leg3/C-Leg4"). During the last phase of the trial, the participants will be returned 
to their original knee. The physical therapy (2 mandatory + one optional session) will be offered 
to ensure that the patient can use properly the mechanical prosthesis. One month follow-up peri-
od, including the measurement of the number of falls, starts once the acclimation criteria are fell-
field. Their preference as well as self-reported tests will be assessed ("2nd A phase - measurement 
with mechanical knee joint"). Finally, participants will be fitted with their original feet after the 
last measurements are conducted. 
The recruitment of the participant will last up to 6 months. Each participant will be enrolled up to 
8 months in the study, depending if the socket and foot are appropriate. The entire flow is de-
scribed in the figure 1, while the physical therapy and fitting concept in the figure 2. 
During each baseline and follow-up visit, approximately 1.5 hours will be needed to complete the 
testing. Four hours will be needed for fitting new socket, foot and foam cosmesis, two hours for 
fitting of MPK and 1 hour for re-fitting a mechanical knee joint. 
Planed duration of the study is from 01.02.2016 until 31.12.2017. 
Blinding of the participants, assessors and statistician 
This will be the first clinical study concerning exo-prosthetic knee joints with both, the partici-
pant and the assessor, blinded. The blinding of participants is possible since appearance charac-
teristics and performance features of C-Leg3 and C-Leg4 are similar. The prostheses will have 
same color, shape and no labeling. In addition each participant will be fitted with the foam cos-
mesis. 
The research center will delegate the role of assessor to one trained employee. The assessor will 
be responsible for evaluating functionality of participants in the performance based tests in all 
phases of the study. During all performance tests, subjects will be instructed to wear long, wide 
trousers which will disable the assessor to see the prosthesis and to refrain from giving any com-
ments. 
The certified prosthetist and physical therapist cannot be blinded. To fit the knee, adjustments 
must be made during walking and knee specific rehabilitation sessions; these procedures cannot 
be carried out in a blinded manner. 
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The randomization procedure will be concealed from all people involved in the study. The order 
of the prosthetic fitting and the device fitted will be concealed from the statistician, which will 
enable blinding of the data analyses. Unmasking will be conducted after completion of the data 
analysis. 
C-Leg4 
Socket ,rnd foot fits 
1" Baseline measmements \\·ith 
NMPK befo1e physical the1apy 
NMPK 
Physical therapr 
2nd Baseline measurements with 
NMPK 2 weeks afte1 
Randomization 
C-1.f'gl 
Filling & Physical the, apy 
Fitting & Physical the1apr 
C-Legt, 
C-Lcg3 
Acclimation period max 90 days 
Acclimation per iocl max 90 days 
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C-1.egt, 
follow up measurements 
C-Leg3 
Fitting & Physical therapy 
C-LegJ 
Acclimation pe1iod 30days 
C-LegJ 
Follow up lllt'aSlllt'lll!"lllS 
NMPI< 
C-Legl 
Follow up measmements 
C-Legti 
Filling & Physical therapy 
C-Leg4 
Acclimation period 30 days 
C-Leg'• 
f.ollow up 111tasu1 e111t•n1s 
Re Filling & Physical the,apy 
NMPK 
Acclimation pe1iod JO days 
NMPI< 
I ol!O\, up 111cas111cmc•nts 
NMPK 
Re fitting of tht> 01 iginal foot 
Fig.1 - Patient flow during the entire study 

Post-market study ,,C-Leg" 
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Dayl 
DayX 
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NMPK 
Mo111111g uainmg session 
Afte1noon t1ain111g session 
Possible uaining session if 
1 equested bv the use1 
Oayl 
Oay2 
Oay3 
DaylO 
DayX 
1st MPK 
Fitting of the C Leg3/ 4 
Afternoon ttaining session 
MO! ning uaining session 
Afternoon t1aining session 
Morning uaining session 
Fitting adjustment and naming 
session 
Possible uai.ning session if 
requested by the usc1 
ottobock. 
2ndMPK 
Oayl I Crossove1 fitting of the C Leg4 / 3 
Afternoon t1aining session 
Oay2 I Fitting adjustment and training 
session 
Day XI 
Possible uaining session if 
requested by the use1 
Fig.2: Physical therapy and fitting concept 
NMPK 
Day 1 L
Re·fitting of the NMPK 
Afternoon training session 
Day2 
Fitting adjustment and uaining 
session 
DayX 
Possible training session if 
1 equested by the use1 

Post-market study ,,C-Leg" 
Version 1.0, 15.12.2015 
6.2 Outcome measures 
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The data on the following outcome measures will be collected at the four assessments: 
Performance based tests 
6 minute gait test 
10 meter gait test 
Stairs Assessment Index (SAi) 
Hill Assessment Index (HAI) 
Four Step Square Test (FSST) 
Self-reported tests 
Activities-specific Balance Confidence (ABC) 
Scale* 
Prosthetic Limb Users Survey of Mobility 
(PLUS-M) 
Amputee Body Image Scale (ABIS) 
Number of stumbles and falls 
Preference of the knee 
* instrument validatP.d in German 
Primary outcome - Level walking 
A phase · 
mechanical 
knee joint 
v 
v 
v 
v 
v 
v 
v 
v 
v 
B phase • 
C phase· 
2nd A phase· 
C-Leg4 or 
C-Leg3 or 
mechanical 
C-Leg3 
C-Leg4 
knee joint 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
v 
Walking endurance (assessed with 6min gait test) and walking speed (assessed with 10m gait 
test) are two important aspects of walking capacity, which is in many groups of patients impaired. 
6 minute gait test (6MGT) 
The 6 MWT is assessment of the walking endurance and it is associated with aerobic capacity due 
to the cardiorespiratory strain of completing this test. In this test the participant should walk 
without physical assistance and cover as much ground as possible during 6 minutes. 
Despite the fact that level walking was extensively tested within the studies where participants 
transitioned from mechanical to microprocessor controlled knee joint, the 6 MWT has never been 
assessed in this setting. 
As shown by Resnik et al., (2011) test-retest reliability (ICC) for unilateral lower-limb amputees is 
0.97, while Minimal Detectable Change (MDC) is 45.0 m. Calculation is based on results of 44 
participants ( mean=332 ± 115m; range 112m to 538m). 
Harada et al, (1999) proved test validity in elderly population (mean age=75 years) with gait 
speed (r = -0. 73) and excellent test-retest reliability (r = 0.95). In same population Perera et al., 
(2006) determined the MDC of 58.31m. Normative data for elderly population (60-69 years old) 
is 572 m on average for males and 538 m for females (Steffen et al, 2002). 
Eright et al., (1998) established reference equations for prediction of the total distance walked 
during six minutes for healthy adults (based on the results from 117 healthy men and 173 
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healthy women, aged 40 to 80 years). The median distance walked was 576 m for men and 494 m 
for women. The 6MGT was significantly less for men and women who were older and heavier, and 
for shorter men. The resulting gender-specific regression equations explained about 40o/o of the 
variance in the distance walked for healthy adults. The suggested equations are: 
6MWD (for healthy men)= (7 .57 x heightcm) - (5.02 x age) - (1. 76 x weightcrn) -309m 
6MWD (for healthy women)= (2.llx heightcm) - (2.29 x age) - (5.78 x weightcm) + 667m 
10 meter gait test (lOmGT) 
The participant is instructed to walk 10 meters, while the time is measured for the intermediate 6 
meters. The participant first walks at a fastest self-selected walking speed. A trial at a maximum 
safe speed is conducted afterwards. For each speed three trials are collected and the average of all 
three trials is calculated. 
While the 6MGT is associated with aerobic capacity because of the cardiorespiratory strain of 
completing this test, the lOmGT requires a brief and maximal effort and would, therefore, be ex-
pected to be associated with muscle strength (Dalgas 2012). 
This test is chosen for several reasons. First, as previously established, a distance-based test is 
preferred to a time-based test because distance-based tests provide the benefit of a target goal. 
Second, during this test, gait initiation and termination occur very close one after the other, plac-
ing primary emphasis on these more complex aspects of gait. Numerous studies have demonstrat-
ed that in the presence of neuromusculoskeletal pathology, changes in motor planning, step 
length, push-off force, and other parameters adversely affect the initiation and termination of gait 
(Kahle et al., 2008). Finally, 6 mis the approximate distance of two lanes of traffic. 
Kahle et al., reported the results for l0mGT for fastest walking speed for 19 transfemoral ampu-
tees for C-Leg (1.27 ± 0.42 m/s) and mechanical knee joints(l.05 ± 0.36 m/s). 
Bohannon et al., (1997), reported excellent test-retest reliability for comfortable and fastest gait 
speeds (ICC= 0.93 - 0.91) in healthy adults (n=230, age 20-79). Normative data for this popula-
tion are presented in the table below: 
Male 
Female 
Age 
Comfortable 
Fast 
Comfortable 
Fast 
20's 
1.39 
2.53 
1.41 
2.47 
30's 
1.46 
2.45 
1.42 
2.34 
40's 
1.46 
2.46 
1.39 
2.12 
SO's 
1.39 
2.07 
1.40 
2.01 
60's 
1.36 
1.93 
1.30 
1.77 
?O's 
1.33 
2.08 
1.27 
1.74 
*Comfortable/ fast gait speed in meters/ second for male and females by decade 
Perera et al, (2006) published MDC=0.13m/s for elderly population. 
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Secondary outcome 
For safety: 
Four Step Square Test (FSST); 
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The aim of the FSST is to complete a stepping sequence through the 4 squares as quickly as possi-
ble. The fastest times on the FSST are done when the participant is able to face the same direction 
for the entire sequence, which involves stepping forward, backward, and sideways to the left and 
right. The FSST score of 24s or more is associated with an increased risk of having multiple falls 
(Dite et al., 2007). 
According to Diet et al (2007) normative data for the transtibial amputees who have higher inci-
dence of falling is 32.6s, while non-fallers mean FSST is 17 .6s. 
Test has excellent test-retest reliability (r = 0.98) in elderly population and concurrent validity 
with the Timed Up and Go test (r = 0.88) (Dite et at., 2002). 
Activities-specific Balance Confidence (ABC) Scale 
The ABC Scale is a self-report measurement to assess balance confidence in performing 16 ambu-
latory activities. Each item is rated on a rating scale that ranges from 0o/o to l00o/o where 0o/o 
means absolutely no confidence and l00o/o represents complete confidence. The average score for 
all 16 items is calculated. 
Powell & Myers et al., (1995) showed excellent test-retest reliability (r = 0.92) in elderly popula-
tion. Normative data for the community dwelling older adults (n = 168, mean age = 70.96) is 
79.89 (Huang & Wang, 2009). Validity of the test is established in the same population through 
excellent correlation between ABC score and Berg Balance Scale (BBS) (r = 0.752) and between 
ABC score and Timed Up & Go Test (TUG) (r = 0.698). 
Self-reported Number of stumbles and falls 
With regard to the study objective, the number of stumbles and falls will be evaluated during the 
last month (30days) that each of the studied devices is used. In practice, a log book will be given 
to the patient to note all falls and stumbles as well as the circumstances around these events, 
which will make it easier for the investigator to analyze them. During the baseline measurements 
the users will be asked to recall number of stumbles and falls, since the log book will be provided 
to the participant when they enter the study. The investigator will note the number of stumbles 
and falls that occurred during the last month of use for each of the studied devices in every case 
report form. 
For stair and hills mobility: Stair (SAi) and Hill (HAI) Assessment Index 
Stair ascent and descent ability will be measured by using the Stair Assessment Index (SAi). Par-
ticipants are asked to ascend and descend a 12-step Americans with Disability Act compliant 
stairwell as they are scored for functional independence and technique by using the 14-level SAi 
scale. Similarly, users' ability to ambulate a decline will be measured with a custom Hill Assess-
ment Index (HAI). Participants are asked to ambulate on a Sm, 5° downgrade hill at self-selected 
speed. Participants are scored for independence, technique and step length by using the 12-level 
HAI scale. Time needed to descent stairs and ramp will be recorded. 
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The HAI had very good interrater reliability in transfemoral amputee population (intraclass corre-
lation coefficient = 0.97 for NMPKs and intraclass correlation coefficient = 0.99 for C-Leg). HAI 
score ranged from 3 to 11 (mean=7.6) for NMPK, and from 5 to 11 (mean=8.9) for C-Leg (High-
smith et al., 2013). 
The SAi was reported for transfemoral amputees walking on NMPK (for K2 mean=3.3, for K3 
mean=4.4) and for C-Leg4 (for K2 mean=9, for K3mean=l0.l) (Hafner et al., 2007). 
For activities of daily living: Prosthetic Limb Users Survey of Mobility (PLUS-M) 
The PLUS-M questionnaire measures prosthesis users' mobility (i.e., their ability to move inten-
tionally and independently from one place to another). The 12 questions assess respondents' 
perceived ability to carry out specific activities that require use of both lower limbs and cover 
movements that range from basic ambulation (e.g., walking a short distance indoors) to complex 
activities (e.g., hiking for long distances over uneven ground). 
Normative data for PLUS-M for transfemoral amputees with dysvascular ethology is 42.9 (n=120), 
with trauma 50.5 (n=266), for mobility grade K2 45.2, for K3 50.5, and for K4 53.8 (n=199). 
PLUS M showed high test reliability (0.96) (Hafner et al., 2015). PLUS-M demonstrated a strong 
positive relationship with the PEQ-MS (r = 0.76) and ABC (r = 0.81) (Gaunaurd et al., 2015) 
For satisfaction and preference: 
Amputee Body Image Scale (ABIS) 
The ABIS assesses how an amputee perceives and feels about his or her body experience. The 
scale addresses several different domains, including: 1) body appearance; 2) body function; 
3effective distress; and 4) behavioral avoidance in social situations. The scale produces scores 
that range from 1 to 100, with low scores indicating the relative absence of a body image concern 
and higher scores indicating the presence of a more serious body-image concern. 
ABIS is proven to be reliable by evaluating the internal consistency of a test instrument (alpha 
coefficient of 0.80). Reported ABIS data for the transfemoral group (n = 30) had a median of 35.5. 
(Breakey et al., 1997). 
Knee Preference 
The user's knee preference is assessed with the question: "Which prosthesis do you prefer?" 
7 
Patient population 
Unilateral subjects having transfemoral amputation or knee-disarticulation will be enrolled in the 
study. 
Inclusion criteria: 
-
Person is > 18 years old. 
-
Person is a unilateral transfemoral or knee-disarticulation amputee with stabilized residu-
al limb. 
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-
Person is a K2, K3 or K4 ambulator based on Medicare Functional Classification Level 
(MFCL) (see appendix). 
-
Person is currently fitted with a prosthesis using a non-microprocessor controlled pros-
thetic knee for at least 6months. 
-
Person was never fitted with microprocessor controlled prosthetic knee joint. 
-
Person is willing and able to independently provide informed consent. 
-
Person is willing to comply with study procedures. 
-
Person wears prosthesis daily and? 8 hours/day. 
-
Person is walking on average lkm/day. 
-
Person is walking not slower than 3km/h (-0.8m/s) (based on 10m walk test conducted 
during recruiting). 
-
Person is walking on level ground alternating steps (step over step manner). 
Exclusion criteria: 
-
Person is under 18 years of age. 
Person who weigh more than 136kg. 
Person who weigh less than 50kg. 
Person who is pregnant. 
Person has a history of chronic skin breakdown on the residual limb. 
Person has conditions that would prevent participation and pose increased risk (e.g. un-
stable cardiovascular conditions that preclude physical activity such as walking). 
Person falls ? once a week due to the reasons that could not be corrected by the new pros-
thesis (for ex. problems with vestibular system). 
Person is using under arm axillary crutches or walker. 
Person in an emergency, life threatening situation. 
Person is unwilling/unable to follow instructions. 
Person who is not available to follow the entire study protocol. 
Person who is participating in another study or intends to participate in another study 
during this study' s duration. 
Person who cannot personally provide their consent. 
Person who is not wearing prosthesis 8hours/day on average. 
Person who has a score on 10m walk test at 3km/h (-0.8m/s) (based on 10m walk test 
conducted during recruiting). 
Person who walks on average less that 1km per day. 
Person who is not able to walk on level ground alternating steps (step over step manner). 
Drop out or early termination of the study 
Subjects can withdraw from the study at any time and for any reason. In case of early termination, 
the investigator must document the reasons as completely as possible. The investigator can tem-
porarily or permanently discontinue the subject's study participation for any reasons that are in 
the subject's best interest, particularly in cases of serious adverse events. If a subject is lost to 
follow-up, the investigator will use all available means to get into contact with him or her. After 
three weekly telephone reminders, the subject will be recorded as lost to follow-up. 
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The investigator will fill in the reason for the drop out or early termination of follow-up in the case 
report form. 
8 
Statistics 
8.1 Number of patients & study sites to enroll and rationale 
Since the primary outcome measure 6MGT will be used for the first time in this setting, the num-
ber of patients who will be enrolled in the study cannot be calculated prior to study beginning. 
Twenty patents who fulfill inclusion/exclusion criteria, will be initially recruited and will follow 
the above described study design. Based on the 6MGT results from these twenty participants the 
total number of patients to be enrolled will be calculated. 
Relaying on an approximated normal distribution, the following formula is used for cross-over 
design studies (Jones, B. and Kenward, M. 2015): 
n = 2 * (a2/li2) * (z(a'/2)+z(~))2 + z(a'/2)2/2 
where, 
a= 0.05 
a' = Bonferroni-adjusted a 
1-~ = desired power, ~=0.80 
a = standard deviation (within-patient) 
Ii = expected difference 
The potential dropout rate of 25o/o during the study will be taken into account when calculating 
the necessary patient number to compare prostheses. 
8.2 Method used to take into account missing, unusable or invalid data 
If data are missing, illegible or incoherent, requests for further information will be sent to the in-
vestigator in question. Computerized data validation programs will be developed and implement-
ed to ensure the database's consistency and validity. If errors or inconsistencies are detected, re-
quests for further information will be sent to the investigator in question; any changes will then 
be integrated into the database by the person in charge. 
8.3 Populations for analysis 
The analysis will be performed on the intention-to-treat (ITT) population and then on the per-
protocol (PP) population. The ITI population is defined as all the patients randomized into their 
randomization group, regardless of the treatment received or their outcome in the study. The PP 
population is defined as all the patients in the ITT population without any major protocol devia-
tions_ 
8.4 Statistical analyses 
Patient characteristics: Quantitative variables will be summarized using standard descriptive sta-
tistics (average, standard deviation, median, minimum and maximum, first and third quartile). 
Qualitative variables will be described using group sizes and frequencies. When relevant, 
95o/oconfidence intervals will be given. Patient characteristics at enrolment will be presented and 
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compared in each group to ensure the groups are initially comparable. The features of any pa-
tients lost to follow-up will be studied. 
Analysis of primary and secondary outcome measures: For the outcomes being evaluated, the 
below listed assessment is considered as the "final point": 
-
after 2nd base line measurements with non-microprocessor controlled knee prosthesis 
-
after up to 90 days of the first MPK prosthetic use when the user is filly accommodated 
-
after 30 days of the second MPK prosthetic use 
-
after 30 days of use of the non-microprocessor controlled knee prosthesis 
To evaluate the primary objective, the 6MGT and l0mGT results will be compared between the 
three prostheses. 
Because this study uses a cross-over design, the potential carry-over effect will be tested to deter-
mine if an interaction exists between the three prostheses using a paired Student's t-test. If the 
effect is significant, only the first period will be analyzed using a paired Student's t test or the 
non-parametric Wilcoxon test if the normality and homogeneity of variances assumptions are not 
met. If the effect is not significant, the period effect and prosthesis effect can then be tested using 
repeated-measures AN OVA or Friedman's AN OVA if the normality and homogeneity of variances 
assumptions are not met. If Friedman's ANOVA is significant, a series of Wilcoxon Signed-ranks 
tests will follow-up with manual Bonferroni correction. 
To evaluate the secondary objectives, the prostheses will be compared on the following criteria: 
-
Four Step Square Test time 
Stair (SAi) and Hill (HAI) Assessment Index score 
Activities-specific Balance Confidence (ABC) Scale score 
Self-reported Number of stumbles and falls 
PLUS-M score 
Amputee Body Image Scale (ABIS) score 
Knee Preference 
The same process will be used for the secondary outcome (Four Step Square Test, Stair (SAi) and 
Hill (HAI) Assessment Index, Activities-specific Balance Confidence (ABC) Scale, Self-reported 
Number of stumbles and falls, PLUS-M and Amputee Body Image Scale (ABIS)) as for the analysis 
of the primary outcome measure. Because this study uses a cross-over design, the potential carry-
over effect will be tested to determine if an interaction exists between the prostheses. If there is no 
significant interaction, the period effect and prosthesis effect will then be tested. If there is a sig-
nificant effect, only the first period will be analyzed. The knee preference will be expressed in 
percentages. 
9 
Study sites and patient recruitment 
The study will start with two sites, one in Austria - Orthopedic Rehabilitation Center SKA Zicksee 
and one in Belgium - Physical Medicine and Rehabilitation Clinic UZ Leuven. Each site will re-
cruited up to 10 participants. The recruitment of study participants for the Austrian study site will 
be carried out by the Pl, who will offer the enrolment to the study to patients treated at Rehabilita-
tions Center SKA Zicksee (see inclusion criteria). The recruitment of study participants for the Bel-
gian study site will be done by Pl, who will phone and have a consultation with former patients of 
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Clinics for Physical Medicine and Rehabilitation, UZ Leuven. Enrollment period of initial 20 par-
ticipants will be 6months, but can be extended if insufficient number of patients is recruited. 
Depending on the estimated sample number is calculated additional study sites and patients will 
be enrolled. The responsible ethic committees will be informed about enrolment of additional 
number of sites/patients via amendment. 
10 Randomization 
The randomization will be performed in random permutated blocks by allocation order. A ran-
domization sequence will be integrated into the electronic case report form so as to define the 
randomized treatment order (C-Leg3 or C-Leg4) and provide the investigator with this information 
during the enrolment visit. 
# 
Research site 
Number of subjects to enroll 
1 
Rehabilitations center SKA Zicksee 
10 
Prim. Priv. Doz. Dr. Stephan Domayer, PhD 
2 
Physical Medicine and Rehabilitation Clinic UZ Leuven 
10 
Dr. Charlotte Kiekens 
11 Risk benefit analysis 
According to external adverse event databases the most prominent risk that comes with the use of 
MPCK is the risk of falling. This is in agreement with the published literature suggesting that the 
amputee population presents an increased risk of falling. Therefore these patients demand a high 
level of safety to be provided by the prosthesis they are supplied with. 
In the study of Hafner et al (2007) participants reported that frequency of stumbling was reduced 
by 25o/o, frequency of semi-controlled falling by 17o/o and frequency of uncontrolled falling by 
l0o/o with C-Leg compared to NMPKs. Also Hafner et al (2009) observed improvements in safety 
with C-Leg compared to NMPKs: for K3 population, significant reduction of stumbles and for K2 
population significant reduction of uncontrolled falls. These findings are supported by the study 
of Kahle et al (2008) where the number of self-reported stumbles decreased by 59o/o and the num-
ber of self-reported falls decreased by 64o/o. 
Beside the studies described above, Highsmith et al (2010) analyzed four additional studies on 
safety in his review article. Three of them reported significantly improved balance with C-Leg 
compared to NMPKs. The study of Hellmann et al (2010) observed that C-Leg never collapsed 
compared to NMPKs during all tested condition such as walking, sudden stopping, sidestepping, 
stepping on object and tripping by disrupting swing extension. In summary, the authors conclud-
ed that users should experience a reduction in stumble and fall events together with improved 
balance as a result of receiving C-Leg (Highsmith et al 2010). 
Since their market introduction in 1997, over about 51 500 Otto Bock C-Legs were sold. Regard-
ing 7 53 critical reclamations recorded internally since 2002 and 19 adverse events recorded ex-
ternally since 1997 the overall incidence rate is rather small (1.5o/o). Secondary, the reviewed 
literature suggests that subjects fitted with a C-Leg not only experience an improvement in per-
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formance and satisfaction but also have a reduced risk of falling. Therefore, the risks associated 
with the use of the device are acceptable when weighed against the benefits to the patient. 
12 Management of adverse events 
12.1 Definitions 
Adverse event (AE): any untoward sign in a person who participates in biomedical research, 
whether or not it is considered related to the study or to the experimental device being studied. 
Serious adverse event (SAE): the event is considered serious if it results in any of the following 
outcomes: 
-
Death 
-
Life-threatening (immediately life threatening at the time of the event and independent of 
the consequences of a corrective or palliative treatment) 
-
Disability or permanent impairment 
-
Hospitalization 
-
Prolongation of existing hospitalization 
-
Congenital deformity/anomaly 
-
Potentially serious event (adverse clinical event or laboratory result that is serious or con-
sidered as such by the investigator). 
Adverse reaction (AR): any untoward and undesirable reaction related to an experimental device 
or any incident that could have led to this reaction in a study participant or a device user if ap-
propriate measures had not been taken. 
Serious adverse reaction (SAR): serious adverse reaction that is attributable to an experimental 
device. 
Unexpected adverse reaction (UAR): adverse reaction where the nature, severity, intensity or pro-
gression is not consistent with the information included in the instructions for use or instruction 
manual if the device is CE marked and in the protocol or investigator's brochure if the device is 
not CE marked. 
lmputabilitv: relationship between the AE and the device being studied. If an AE is related to the 
experimental device, it becomes an AR. The following factors will be taken into account when 
determining imputability: 
-
Sequence of events 
-
The AE resolves when the device is removed and/or reappears when it is put on again 
-
Knowledge of a similar historical event during the use of the device or a device in the same 
class 
-
Existence of another etiology. 
Severity: The severity of the AE will be evaluated by the investigator based on the following classi-
fication: 
-
Grade 1 - Minor: AE that is generally transient and has no after-effects on normal activities 
-
Grade 2 - Moderate: AE that is troublesome enough to affect normal activities 
-
Grade 3 - Serious: AE that considerably modifies the patient's normal activity routine, or 
that is disabling or life threatening. 
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Any Note: The severity criteria must not be confused with the seriousness criteria that serve as a 
guide for defining declaration requirements. 
12. 2. Investigator's role 
During the entire patient follow-up period, any AE that occurs to a person during the study period 
must be followed until it resolves or is deemed permanent. The investigator must explore the pos-
sibility that an AE has occurred at each follow-up visit. 
Any AE, regardless of whether it is related to the study, must be documented. Any change in the 
severity, relationship with the medical device, procedures required to treat the event or progres-
sion must be monitored and documented. 
Any SAE, no matter its causal relationship with the studied device must be declared to the spon-
sor on the form provided for this purpose in the case report form within 24 hours of its occurrence 
(or as soon as the investigator becomes aware of it). The initial declaration may be followed by 
relevant additional information within 7 days. 
12.3. Sponsor's role 
The sponsor evaluates the causal relationship of the AE, any adverse event where the investigator 
or sponsor believes that a causal relationship with the experimental device may reasonably be 
expected, is considered as a suspected adverse reaction. If the sponsor and investigator have dif-
fering assessments, both opinions will be listed on the declaration sent to the competent authori-
ty, if this declaration is needed). 
13. Monitoring of clinical trial 
The study site is required to conduct the study in accordance with the protocol, all applicable 
laws and Federal regulations and any conditions or restrictions imposed by the reviewing ethics 
committee. The Clinical Project Manager will ensure proper monitoring of the study with special 
attention to verification of all clinical requirements, adherence to protocol, good clinical practices 
and compliance with applicable government and institutional regulations. The investigator will 
provide the monitor access to all necessary records to ensure the integrity of the data. 
13.1 Study monitors 
The investigation will be monitored on a continuing basis through the course of the clinical trial. 
The Clinical Project Manager will serve as clinical monitor. 
13.2. Site visits 
Site initiation visits will be made by the Clinical Project Manager to review the study protocol and 
documentation requirements with the investigator and hospital support staff involved with the 
study. The project manager will ensure that all researchers involved in the project have adequate 
training. 
Ongoing monitoring visits of the investigational center(s) will be conducted to compare the data 
recorded in the CRFs with the information contained in the original source documents (source 
data verification). For the following items, this check will be lOOo/o: 
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participant's identification number 
-
participant signed informed consent obtained 
-
participant's eligibility criteria (inclusion and exclusion criteria) 
-
efficacy variables 
-
medical record of Adverse Events 
For all other items, at least 20o/o of the data will be checked. 
ottobock. 
Additional management of the clinical sites will be achieved by communications via letter, fax, 
electronic mail and/or telephone. 
Site close-out visit will be conducted after all subjects have been enrolled and follow-up has been 
completed or if deemed necessary. 
13.3. Data collection & review 
Two forms of CRF will exist: electronical CRFs for Investigators and Assessors and paper CRFs for 
prosthetists and physical therapists. The reason for this is separation is that treatment will be 
concealed from assessor but not from prosthetist and physical therapist and secondly to ease the 
data collection data analysis. 
An electronic case report form (eCRF) will be developed by eClinicalOS (Merge, 4000 Aerial Center 
Parkway, Suite 101 Morrisville, NC 27560). 
The CRFs are created in English, but the questionnaires: Activities-specific Balance Confidence 
(ABC) Scale, PLUS-M score, Amputee Body Image Scale (ABIS) and patient's logbook are translat-
ed in the country's local language. 
CRFs must be completed after every visit for each subject enrolled into the study. All forms must 
be filled out completely. An explanation must be provided for any missing data points. Correction 
of data in the paper CRFs should be made by crossing out the incorrect data with a single line and 
writing the correct values next to those crossed out. Incorrect entries must not be obliterated. 
Each correction must be initialed and dated by the person making the correction. All CRFs must 
be signed and dated: electronical by the principal investigator, and paper ones by responsible 
prosthetist or physical therapist. 
All CRFs will be reviewed for completeness and clarity. Queries for missing or unclear data will be 
made as necessary throughout the study. Otto Bock Healthcare Products GmbH may request fur-
ther documentation such as physician notes when complications or malfunctions are observed 
and reported. 
The Clinical Projects Manager will ensure that the study is properly implemented according to the 
procedures defined in the protocol and in accordance with Good Clinical Practices, along with 
applicable regulatory measures. 
The Clinical Projects Manager will visit each center in order to: 
-
Check if the protocol is being followed 
-
Verify if all AE and SAE have been declared 
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The investigators commit to allowing audits to be performed by the sponsor and to potential in-
spections being performed by competent authorities. All data, documents and reports can be the 
subject of audits and regulatory inspections. 
14. Study Discontinuation 
14.1. Investigational Site Termination 
Otto Bock Healthcare Products GmbH reserves the right to terminate an investigational site for 
any of the following reasons: 
• Failure to secure Informed Consent from a subject enrolled into the study 
• Repeated protocol violations 
• Repeated failure to complete Case Record Forms on a timely basis 
• Failure to report Adverse Events on a timely basis 
• The investigator requests discontinuation 
If the study is prematurely terminated or suspended for any reason, study participants will be 
informed promptly and, where required by the applicable regulatory requirement(s), the relevant 
regulatory authority(ies) will be informed. The ethics committees will be informed promptly and 
provided with a detailed written explanation for the termination or suspension. 
14.2. Premature Discontinuation of the complete study 
If the study is prematurely terminated or suspended, the Project Manager, on behalf of Otto Bock 
Healthcare Products GmbH, will inform promptly the investigator/institution, and, if applicable, 
the regulatory authority(ies) of the termination of suspension and the reason(s) for the termina-
tion or suspension. The ethics committees will be informed promptly and provided with a detailed 
written explanation for the termination or suspension by the Project Manager, on behalf of Otto 
Bock Healthcare Products GmbH, or by the investigator/institution, as specified by the applicable 
regulatory requirement(s). Some of the reasons for premature termination of the study are: 
• if the safety of the participants is jeopardized (eh. many falls and stumbles reported), and 
• if the users can not show "proficient use" of the intervention devices (e.g. users are not 
able to ambulate on even and uneven terrain, stairs, hills, and to use their prosthesis in 
everyday life in the same extend as shown during the recruitment). 
15. Ethical considerations 
15.1. Research ethics committee 
In accordance with current laws of the countries where study will be conducted, the protocol will 
be submitted to the Research Ethics Committee for an opinion. No patient can be enrolled before 
the authority has approved the study and the sponsor has held the study launch meeting. 
15.2. Patient information and consent 
Patients will be informed completely and honestly, using easily understood language, of the ob-
jectives and constraints of the study, the potential risks faced, required monitoring and safety 
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measures, their right to refuse to participate in the study and the possibility of withdrawal at any 
time. 
All of this information is included on the information sheet and consent form given to the patient. 
The patient's free, informed and written consent will be collected by the investigator before en-
rolment in the study. A copy of the information and consent form, signed by both parties, will be 
given to the patient; the investigator will keep the original form. At the end of the study, a copy 
will be placed in a tamperproof sealed envelope containing all of the consent forms; this envelope 
will be archived by the sponsor. 
15.3. Subject compensation 
All subjects participating in this pilot study will receive refund for their travelling costs and time 
expenditure (15€/ hour during the visits - 660€ intotal). The remuneration shall be assigned in 
an all-inclusive payment upon completion of the study. 
Otto Bock Healthcare Products GmbH will provide sockets, carbon spring feet, microprocessor 
controlled knee joints (C-Leg3 and C-Leg4) and foam cosmesis. The participants will have the 
opportunity to keep the sockets and cosmesis, while the knees and feet will be returned to the 
manufacturer. 
15.4. The clinical investigator 
The Investigator must fulfil all requirements as stated in ISO 14155-1, Good Clinical Practice 
(GCP) and law of the country where the study is conducted. He/she is responsible for the conduct 
of the clinical trial and is responsible for the clinical well-being of the subjects involved. 
16. Disclosure of data and publication policy 
By signing the final protocol, every participating investigator agrees to keep all information and 
results concerning the study and the investigational product confidential. The confidentiality 
obligation applies to all personnel involved at the investigational site. Public presentation of 
study results requires mutual agreement between the investigator(s) and Otto Bock Healthcare 
Products GmbH. 
Otto Bock Healthcare Products GmbH may disclose data derived from the study to other investiga-
tors and domestic or foreign regulatory authorities. 
All patient related data are recorded in a pseudonymized manner. 
The originals of the completed CRFs will be collected by monitor during monitoring visits or sent 
to the project manager after each assessment with each subject. Copies of completed CRFs and 
documentation of Informed Consent will be retained by the Investigator together with the sub-
jects' notes. 
Copies of all study documents will be retained by the Otto Bock and investigator for 15 years fol-
lowing the end of the study or earlier if approved by Otto Bock. 
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17. References 
ottobock. 
Abellan van Kan G, Rolland Y, Andrieu S, et al. Gait speed at usual pace as a predictor of adverse outcomes 
in community-dwelling older people. J Nutr Health Aging. 2009; 13(10):881-889. 
Bellmann, Malte; Schmalz, Thomas; Blumentritt, Siegmar {2010): Comparative biomechanical analysis of 
current microprocessor-controlled prosthetic knee joints. In: Arch Phys Med Rehabil 91 (4), S. 644-652. 
Bohannon, R. W. {1997). "Comfortable and maximum walking speed of adults aged 20-79 years: reference 
values and determinants." Age Ageing 26(1): 15-19. 
Breakey: Body Image: The Lower-Limb Amputee JPO 1997 Vol. 9, Num. 2 pp. 58-66 
Dalgas U, Severinsen K, Overgaard K. Relations between 6 minute walking distance and 10 meter walking 
speed in patients with multiple sclerosis and stroke. Arch Phys Med Rehabil. 2012 Jul;93{7):1167-72. doi: 
10.1016/j.apmr.2012.02.026. Epub 2012 Mar 12. PubMed PMID: 22421626. 
Dite, Wayne; Connor, Helen J.; Curtis, Heather C. {2007): Clinical Identification of Multiple Fall Risk Early 
After Unilateral Transtibial Amputation. In: Arch Phys Med Rehabil 88 (1), S. 109- 114. DOI: 
10.1016/j.apmr.2006.10.015. 
Dite, W. and Temple, V. A. {2002). "A clinical test of stepping and change of direction to identify multiple 
falling older adults." Arch Phys Med Rehabil 83(11): 1566-1571. 
Drerup, B.; Wetz, H. H.; Bitterle, K.; Schmidt, R. {2008): Langzeitergebnisse mit dem C-Leg - Ergebnisse 
einer retrospektiven Studie. Long Term Results with the C-Leg - Results of a Retrospective Study. In: Or-
thopadie-Technik 3, S. 169-17 4. 
Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care 
Med. 1998 Nov;158(5 Pt 1):1384-7. PubMed PMID: 9817683. 
Gaunaurd I, Gailey R, Salem R, Hafner B. Construct validity of the Prosthetic Limb Users Survey of Mobility 
(PLUS-M). Proceedings of the 15th World Congress of the International Society of Prosthetics and Orthotics, 
Lyon, France, June 22-25, 2015 
Hafner, Brian J.; Willingham, Laura L.; Buell, Noelle C.; Allyn, Katheryn J.; Smith, Douglas G. {2007): Eval-
uation of function, performance, and preference as transfemoral amputees transition from mechanical to 
microprocessor control of the prosthetic knee. In: Arch Phys Med Rehabil 88 (2), S. 207- 217. DOI: 
10.1016/j.apmr.2006.10.030. 
Hafner, Brian J.; Smith, Douglas G. (2009): Differences in function and safety between Medicare Functional 
Classification Level-2 and -3 transfemoral amputees and influence of prosthetic knee joint control. In: JRRD 
46 (3), s. 417- 433. 
Hafner B, Morgan S, Askew R. Reliability of self-reported outcome measures in people with lower limb loss: 
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18. Appendix 
Medicare Functional Classification Level (MFCL) description 
KO 
Does not have the ability or potential to ambulate or transfer safely with or without as-
sistance and a prosthesis does not enhance quality of life or mobility. 
Kl 
Has the ability or potential to use a prosthesis for transfers or ambulation on level sur-
faces at fixed cadence. Typical of the limited and unlimited household ambulator. 
K2 
Has the ability or potential for ambulation with the ability to traverse low-level envi-
ronmental barriers such as curbs, stairs, or uneven surfaces. Typical of the limited 
community ambulator. 
K3 
Has the ability or potential for ambulation with variable cadence. Typical of the com-
munity ambulator who has the ability to traverse most environmental barriers and may 
have vocational, therapeutic, or exercise activity that demands prosthetic utilization 
beyond simple locomotion. 
K4 
Has the ability or potential for prosthetic ambulation that exceeds the basic ambulation 
skills, exhibiting high impact, stress, or energy levels, typical of the prosthetic demands 
of the child, active adult, or athlete. 
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