Performance and Safety of the Polylactic Interference Screw Used in Anterior Cruciate Ligament Reconstructions
Conditions: Knee Ligament Injury
Sponsor: Biomatlante

 
 
 
 
 
 
 
 
 
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PERFORMANCE AND SAFETY OF THE POLYLACTIC INTERFERENCE 
SCREW USED IN ANTERIOR CRUCIATE LIGAMENT 
RECONSTRUCTIONS 
 
N° ID-RCB: 2018-A03207-48 
Study reference: RE-DT05-18B 
Version N°1.0 dated on 05/07/2019 
PROTOCOL FOR RESEARCH INVOLVING HUMAN PARTICIPANTS  
(Category 3 – Non interventional study) 
 
 
SPONSOR 
BIOMATLANTE SA 
Julien DERT 
5 rue Édouard Belin – ZA Les Quatre Nations 
44360 VIGNEUX-DE-BRETAGNE - FRANCE 
Phone: 02.28.02.00.09 – Fax: 02.28.02.00.10 
E-mail: juliendert@biomatlante.com
REGULATORY CONTACT AT 
THE SPONSOR’S SITE 
Laura PAGNUCCO 
5 rue Édouard Belin – ZA Les Quatre Nations 
44360 VIGNEUX-DE-BRETAGNE - FRANCE 
Phone: 02.28.02.00.09 – Fax: 02.28 02.00.10 
E-mail: laurapagnucco@biomatlante.com 
COORDINATING 
INVESTIGATOR 
Dr François-Xavier VERDOT 
21 Boulevard Karl Marx 
42100 SAINT-ETIENNE - FRANCE 
Phone: 04.77.42.09.86 
E-mail: fxverdot@ortheo.org 
CONTRACT RESEARCH 
ORGANIZATION 
ATLANSTAT 
3 rue Jules Verne 
44400 REZE - FRANCE 
Phone: 02.40.63.16.60 
 
 
 

 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
 
TABLE OF CONTENTS 
3 
PROTOCOL AMENDMENT HISTORY 
5 
VALIDATION AND SIGNATURES 
6 
CLINICAL INVESTIGATOR AND COLLABORATORS 
7 
CLINICAL CENTERS 
7 
LIST OF ABBREVIATIONS 
8 
SYNOPSIS OF THE STUDY 
9 
I. 
SCIENTIFIC JUSTIFICATION AND GENERAL DESCRIPTION 
14 
I.1. 
INTRODUCTION 
14 
I.2. 
CURRENT STATE OF KNOWLEDGE 
14 
I.3. 
RESEARCH HYPOTHESES 
16 
I.4. 
JUSTIFICATION OF METHODOLOGICAL CHOICES 
16 
I.5. 
EXPECTED IMPACTS 
16 
II. 
OBJECTIVES AND OUTCOMES 
16 
II.1. 
PRIMARY OBJECTIVE AND CO-PRIMARY ENDPOINT 
16 
II.2. 
SECONDARY OBJECTIVES AND ENDPOINTS 
17 
III. RESEARCH DESIGN 
17 
III.1. 
CLASSIFICATION OF THE STUDY 
17 
III.2. 
THE RESEARCH PROJECT AGENDA 
17 
III.3. 
SUMMARY TABLE OF THE PARTICIPANT FOLLOW-UP 
18 
III.4. 
INFORMATION OF THE PERSONS CONCERNED 
18 
III.5. 
FOLLOW-UP VISITS 
19 
III.6. 
END OF RESEARCH VISIT 
19 
IV. STUDY POPULATION 
20 
IV.1. 
INCLUSION CRITERIA 
20 
IV.2. 
EXCLUSION CRITERIA 
20 
IV.3. 
FEASIBILITY AND RECRUITMENT PROCEDURES 
20 
IV.4. 
ACTIONS UPON PATIENT WITHDRAWAL 
21 
V. 
TREATMENT/ STRATEGY(IES)/ PROCEDURE(S) OF THE RESEARCH 
21 
V.1. 
DESCRIPTION OF SURGICAL TREATMENT FOR ACL RECONSTRUCTION (HAS 
RECOMMENDATIONS) 
21 
V.2. 
DESCRIPTION OF THE PRODUCT 
23 
V.3. 
INTENDED USE 
23 

 
 
 
 
 
 
 
 
 
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V.4. 
SURGICAL INDICATION 
23 
V.5. 
CHOICE OF TREATMENT IN THE STUDY 
24 
V.6. 
CONTRAINDICATIONS 
24 
V.7. 
AUTHORIZED OF FORBIDDEN TREATMENTS AND PROCEDURES 
24 
VI. STUDY ASSESSMENT AND PROCEDURES 
24 
VI.1. 
MAIN EVALUATION CRITERION 
24 
VI.2. 
SECONDARY EVALUATION CRITERIA 
25 
VI.3. 
MANAGEMENT OF ADVERSE EVENTS 
26 
VII. STATISTICAL ASPECTS 
30 
VII.1. 
SAMPLE SIZE DETERMINATION 
30 
VII.2. 
ANALYSIS SETS 
31 
VII.3. 
MISSING VALUES AND DROP-OUT 
32 
VII.4. 
STATISTICAL ANALYSIS 
32 
VIII. RIGHTS OF ACCESS TO DATA AND SOURCE DOCUMENTS 
36 
VIII.1. 
ACCESS TO DATA 
36 
VIII.2. 
SOURCE DATA 
36 
VIII.3. 
DATA CONFIDENTIALITY 
36 
VIII.4. 
PSEUDONYMIZATION PROCEDURE 
37 
IX. QUALITY CONTROL AND QUALITY ASSURANCE 
38 
IX.1. 
GUIDELINES FOR COLLECTING DATA 
38 
IX.2. 
RESEARCH FOLLOW-UP 
38 
IX.3. 
QUALITY ASSURANCE AND QUALITY CONTROL 
38 
IX.4. 
DATA MANAGEMENT 
39 
IX.5. 
PROTOCOL DEVIATION 
40 
IX.6. 
AUDIT AND INSPECTION 
40 
X. 
ETHICAL AND REGULATORY CONSIDERATIONS 
41 
X.1. 
COMPLIANCE WITH REFERENCE TEXTS 
41 
X.2. 
CHANGES TO THE PROTOCOL 
41 
XI. PRESERVATION OF RESEARCH DOCUMENTS AND DATA 
42 
XII. RULES FOR PUBLICATION 
42 
XII.1. 
SCIENTIFIC COMMUNICATIONS 
42 
XII.2. 
COMMUNICATION OF RESULTS TO PATIENTS 
42 
XII.3. 
TRANSFER OF DATA 
43 
XIII. BIBLIOGRAPHIC REFERENCES 
44 
 
 
 
 

 
 
 
 
 
 
 
 
 
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PROTOCOL AMENDMENT HISTORY 
 
VERSION 
DATE 
DESCRIPTION OF THE MODIFICATION 
N° 1.0 
05/07/2019 
First validated version presented to the Ethical Committee  
 
 
 

 
 
 
 
 
 
 
 
 
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VALIDATION AND SIGNATURES 
 
 
 
SPONSOR 
BIOMATLANTE SA 
Julien DERT 
CEO 
 
REGULATORY 
CONTACT AT THE 
SPONSOR’S SITE 
Laura PAGNUCCO 
Regulatory Affairs Engineer 
 
COORDINATING 
INVESTIGATOR 
Dr François-Xavier VERDOT 
Orthopaedic and Traumatological 
surgeon 
 
CONTRACT 
RESEARCH 
ORGANIZATION 
ATLANSTAT 
Nadine GODFROID 
CEO 
 
 
 

 
 
 
 
 
 
 
 
 
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CLINICAL INVESTIGATOR AND COLLABORATORS 
 
 
COORDINATING 
INVESTIGATOR 
Dr François-Xavier VERDOT 
Orthopaedic and 
Traumatological surgeon 
Address: 21 Boulevard Karl Marx – 
42100 Saint-Etienne 
Phone: 04.77.42.09.86 
E-mail: fxverdot@ortheo.org 
CLINICAL RESEARCH 
COLLABORATOR 
ATLANSTAT 
Nadine GODFROID 
Clinical Operations Manager 
Address: 3 Rue Jules Verne – 44400 
Rezé 
Phone: 02.40.63.16.60 
E-mail: nadine.godfroid@atlanstat.com 
CONTRACT 
RESEARCH 
ORGANIZATION 
ATLANSTAT 
Data Management department 
Biostatistic Department 
Address: 3 Rue Jules Verne – 44400 
Rezé 
Phone: 02.40.63.16.60 
 
 
 
 
 
CLINICAL CENTERS 
 
 
CLINICAL CENTER N°01 
Centre ORTHEO 
21 Boulevard Karl Marx 
42100 SAINT-ETIENNE 
FRANCE
 
 
 

 
 
 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS 
 
ACL 
Anterior Cruciate Ligament 
AE 
Adverse Event 
ANSM 
Agence Nationale de Sécurité du Médicament et des produits de santé 
BPTB 
Bone Patellar Tendon Bone 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CPP 
Committee for Protection of Persons  
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
DLSTG 
Double-Loupe SemiTendinosus and Gracilis 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
EMA 
European Medicines Agency 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
ICH GCP 
International Conference on Harmonisation Good Clinical Practice 
KJ 
Kenneth Jones 
LOCF 
Last Observation Carry Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
PIS 
Polylactic Interference Screw 
PT 
Preferred Term 
PP 
Per protocol 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SOC 
System Organ Class 
SS 
Safety Set 
ST4 
SemiTendinosus 
TEAE 
Treatment-Emergent Adverse Events 
 
 

 
 
 
 
 
 
 
 
 
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SYNOPSIS OF THE STUDY  
 
Title 
Performance and safety of the Polylactic Interference Screw used in Anterior 
Cruciate Ligament Reconstructions 
Sponsor 
BIOMATLANTE SA 
Coordinating investigator 
Dr. François-Xavier VERDOT 
ANSM identification 
2018-A03207-48 
Justification / context 
The evaluation of the clinical data has demonstrated the conformity of the 
Polylactic Interference Screw (PIS), with the relevant essential requirements 
for its use in orthopaedic applications. The Polylactic Interference Screws 
are intended for tibial and femoral ligament/graft fixation in the case of 
Anterior Cruciate Ligament (ACL) reconstructions. It has been concluded 
that the risks associated with the use of this medical device are acceptable 
when weighted against the benefits to the patients.  
In order to improve the clinical data on the PIS, the manufacturer, 
Biomatlante, decided to assess that the performance and safety of the device 
are maintained until the reaching of its intended use. In this objective, the 
goal of this study will be to observe the following parameters: 
1. Objective IKDC score (clinical evaluation), 
2. Subjective IKDC score (functional evaluation) 
3. Safety (report of any adverse event) 
4. Follow-up of the patient’s recovery 
Studied disease 
Rupture of the Anterior Cruciate Ligament 
Puropose of the device 
x Treatment 
o Diagnostic 
o Supportive care 
o Prevention 
o Screening 
o Health services Research 
o Basic science 
o Other 
Study model 
x Single group 
o Parallel 
o Crossover 
o Factorial 
Type of data 
o Safety 
xSafety/Efficacy 
o Efficacy 
o Bio-equivalence 
o Bio-availability 
o Pharmacokinetics 
o Pharmacokinetics/dynamics 
o Pharmacodynamics  
Number of arms  
1 
Medical device used 
OsteotwinTM Polylactic Interference Screw (CE 0123) 
Studied component 
o Drug (including placebo) 
o Radiation 
x Device  
o Behavioural 
o Other 
o Biological / vaccine 
o Genetic 
o Procedure / surgery 
o Dietary supplement 
Classification of the study 
Category 3: Non-interventional study.  
This clinical investigation is prospective, monocentric and intra-subject 
comparative. 
 

 
 
 
 
 
 
 
 
 
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The study is classified as category 3 according to the Jardé Law (French 
Law relative to the Clinical Research Involving Human Persons) and thus is 
qualified as “non-interventional”.  
Indeed, according to the terms of the protocol established in collaboration 
with the stakeholders, this research will be carried out on a CE-marked 
device (CE 0123) and does not involve any risk or constraint since all the 
procedures will be performed and the products used in a usual way, without 
any additional or unusual diagnostic, treatment or monitoring action. 
Intervention description 
Fixation of a ligament/graft in a bone tunnel in order to reconstruct the 
damaged Anterior Cruciate Ligament. 
Surgical technique 
The surgical technique consists on the use of a tendon graft from the 
hamstring muscles:  
- 
DLSTG (Double-Louped SemiTendinosus and Gracilis) technique: use 
of tendon grafts from the Double-Louped SemiTendinosus and Gracilis 
muscles 
- 
ST4 (SemiTendinosus) technique: use of a tendon graft only from the 
SemiTendinosus muscle. 
Primary endpoint measure Evaluation of performance of the PIS in terms of ACL reconstruction by the 
clinical and functional evaluation of the knee. 
Time points at which 
primary endpoint measure 
is assessed 
- 
Pre-surgery (up to 4 months before surgery) 
- 
7 months (± 1 month) post-surgery  
Secondary endpoint 
measure 
- 
Evaluation of safety of the PIS by the record of any adverse event during 
follow-up, especially the one mentioned in the Instructions For Use 
(IFU)  
- 
Follow-up of the patient’s recovery by a visual clinical examination and 
the record of specific objective IKDC items 
Time points at which the 
secondary endpoint 
measure is assessed 
Safety data:  
From screening through visit at 7 months (± 1 month). 
 
Follow-up data:  
2 months (± 2 weeks) post-surgery  
Inclusion criteria 
1. Acute or chronic ACL deficiency with complete or partial lesion of the 
anteromedial bundle requiring primary reconstruction of the ACL with 
hamstring tendons  
2. Males or Females aged 18 to 60 years 
3. No history of surgery on the affected knee 
4. Patients not under guardianship or judicial protection 
5. Signature of non opposition form (consent of the patient) 
Exclusion criteria 
1. History of ligament, meniscal surgery or fracture on the affected knee 
2. Pregnancy or breastfeeding women 
Study size 
The sample size required for the study was determined in order to obtain 
sufficient final statistical power considering the 2 main criteria (co-primary 
endpoint). The statistical power used to determine the sample size required 
for each of the 2 main criteria is 90% to obtain a final statistical power of at 
least 80%. 
 

 
 
 
 
 
 
 
 
 
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Subjective IKDC: 
The minimum relevant difference expected in the change at 7 months on the 
functional IKDC score is 11 points and the standard deviation expected in 
the IKDC score at both timepoint is 13 points. A total of 32 evaluable 
patients will be necessary to ensure a 90% power to detect a significant 
difference in the change at 7 months for two-sided test at the 5% level using 
paired Student t test or Wilcoxon test (depend of normality assumption). 
 
Objective IKDC: 
It is expected that 96% of patient will have modalities C or D before surgery 
[5]. Based on the investigator's experience, the proportion of total expected 
to shift from an IKDC modalities C or D to modalities A or B is 70% and 
proportion of total expected to shift from an IKDC modalities A or B to 
modalities C or D is 1%. A total of 11 evaluable patients will be necessary to 
ensure a 90% power to detect a significant difference for two-sided test at 
the 5% level using McNemar test. 
 
In order to ensure sufficient statistical power for both comparisons, the 
larger of the two required sample size is planned to be included, i.e. 32 
patients. 
 
However, to increase the estimate precision of the co-primary endpoint, 50 
completed patients will be targeted. With 50 patients, a precision around 
13% can be achieved for the objective IKDC score and 3.6 points for the 
subjective IKDC score. This sample size will provide a final statistical 
power for primary objective of 97%. 
Accounting for a maximum of 10% dropouts or missing data, 56 patients 
should be recruited in the study. 
Duration of the research 
- 
Duration of the inclusion period: 12 months 
- 
Follow-up period per participant: maximum 12 months (at most 4 
months before surgery and 8 months of follow-up) 
- 
Total research duration: 24 months 
Statistical analysis of the 
data 
A Statistical Analysis Plan (SAP) will be written by the Biostatistician and 
approved and signed by the Sponsor and the Coordinating Investigator 
before the first database lock. 
All data will be presented using descriptive statistics. 
An interim analysis is planned in this study protocol in order to obtain the 
preliminary results for first quarter 2020. 
Quantitative or ordinal variables will be described by the number of values 
entered, the number of missing data, the mean, the standard deviation, 95% 
confidence interval (CI) of the mean, the median, the 1st and 3rd quartiles, the 
minimum and the maximum.  
Qualitative variables will be described by the number of data filled in, the 
number of missing data, the frequency and the percentage of each modality. 
The 95% CIs of the percentages will be performed using exact confidence 
limits method. 
 
The medical and surgical histories and adverse events will be tabulated by 
Medical Dictionary for Regulatory Activities (MedDRA) System Organ 
Class (SOC) and Preferred Term (PT).  
 

 
 
 
 
 
 
 
 
 
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Primary efficacy endpoint 
The co-primary endpoint analysis will be performed on the Full Analysis Set 
(FAS) population. 
The scores recorded at 7 months (±1 month) after surgery will be compared 
to the scores recorded before surgery. The intra-subject comparison will be 
the main judgement criteria of success. 
The objective IKDC score will be dichotomised by combining modalities A 
and B and modalities C and D.  
The objective IKDC score at 7-months visit will be compared to the 
objective IKDC score before surgery using exact McNemar test. 
The subjective IKDC score at 7-months visit will be compared to the 
subjective IKDC score before surgery using paired Student t test or 
Wilcoxon test (depend of normality assumption). 
Sensitivity analyses using different analyses sets and missing data handling 
will be performed as described in section “Missing values / dropouts”. The 
Per Protocol (PP) analysis will be considered as confirmatory analysis. 
Secondary efficacy endpoint 
The visual clinical examination and the record of specific IKDC items 
performed during the 2-months visit will be summarized using descriptive 
statistics on the FAS population. 
Safety analysis 
The safety analysis will be performed on the safety set (SS) population.  
Adverse Events (AEs) will be classified according to period of occurrence: 
pre-treatment AEs, Treatment-Emergent AEs (TEAEs). 
TEAEs will be summarized and detailed by:  
· seriousness,  
· intensity,  
· action taken with trial medication,  
· other action taken,  
· relationship to study treatment,  
· severity according to the relationship 
 
The number/frequency of patients with each TEAE will be displayed by 
System Organ Class (SOC) and Preferred Term (PT) according to MedDRA 
classification.  
All serious adverse events (SAEs) will be listed separately with the same 
information that the TEAE. 
 
All individual data will be presented in listings.  
 
The statistical analysis will be performed using SAS® or equivalent 
software.  
 
No sub-group analysis is planned.  
Expected impacts 
This study will confirm the ability of the PIS to help the reconstruction of 
Anterior Cruciate Ligament and its acceptable benefit/risk balance.  

 
 
 
 
 
 
 
 
 
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Keywords 
Anterior cruciate ligament reconstruction, anterior cruciate ligament rupture, 
knee ligament reconstruction, knee ligament rupture 
 
  
 
 

 
 
 
 
 
 
 
 
 
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I. 
SCIENTIFIC JUSTIFICATION AND GENERAL DESCRIPTION 
I.1. INTRODUCTION 
ACL reconstruction with various strategies and therefore interference screws has become a routine surgery. 
Screws for ACL reconstruction provided by Biomatlante are widely used and their benefit/risk ratio has to 
be confirmed. Safety and performance of this PIS will be assessed in this study during a follow-up of 7 
months (±1 month).  
Moreover, any new information provided within this study may help improving the patients’ health care 
undergoing ACL reconstruction with PIS. 
I.2. CURRENT STATE OF KNOWLEDGE 
From an anatomical point of view, the rupture of the Anterior Cruciate Ligament is characterized, at least in 
case of complete rupture, by their incapacity to heal spontaneously, whether or not there is immobilization 
of the knee. This disability is related to intra-articular Anterior Cruciate Ligament and vascular poverty of 
the ligament. 
The diagnosis of rupture of the Anterior Cruciate Ligament is based on: 
· 
The questioning: notion following a trauma of a crack or a disrobement; 
· 
The clinical examination which is comparative and which seeks to highlight the laxity: Lachman's 
manipulation which objectifies anterior translation of the tibia under the femur at 20° of flexion, 
typically with a soft stop. This manipulation, always feasible even on a freshly traumatized knee, is 
of great specificity and sensitivity; 
· 
Manoeuvring the jump, not feasible on an acute knee, but on a chronic laxity reproduces the 
sensation of instability felt by the patient; 
· 
Anterior drawer at 90° which shows a globalization of laxity. Its absence does not mean an absence 
of ACL rupture [1].  
In the absence of intervention, complete rupture of the Anterior Cruciate Ligament usually leaves a residual 
laxity. 
Regardless of the patient's functional complaint, which is dominated by functional instability, rupture of the 
Anterior Cruciate Ligament is ultimately responsible for secondary meniscal lesions and osteoarthritis. 
Ligament reconstruction of the Anterior Cruciate Ligament is a surgical technique that aims to meet two 
imperatives: 
· 
Stabilize the knee and allow the patient to resume his activities, especially sports (functional result), 
· 
Reserving the future of the knee by limiting the risk of secondary meniscal injury and possibly 
cartilaginous degradation [2].  

 
 
 
 
 
 
 
 
 
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Many techniques of reconstruction of the Anterior Cruciate Ligament (ACL) have been described in the 
scientific literature. One of the weak points of these reconstructions resides in graft fixation systems. 
Since the 1990s, the use of patellar tendon plasty (with a bone bar) is emerging simultaneously with the 
appearance of titanium interference screws. Later, resorbable screws provide mechanical strength identical 
to metal screws but generate inflammatory reactions, a phenomenon described but not quantified in the 
literature. In order to overcome this phenomenon, screws made of PEEK (PolyEtherEtherKetone) make 
their appearances [3]. However, fixation with resorbable interference screws is recognized as gold standard 
for the fixation of the patellar tendon graft according to the Haute Autorité de Santé (HAS) in France [2]. 
One of the most used evaluation methods for assessment of patients’ recovery after ACL reconstruction is 
the objective IKDC score (clinical evaluation) [4]. 
A review of the literature published on the known results of the subjective IKDC score (functional 
evaluation) makes it possible to estimate that the standard deviation around the mean will be about 13 
points in post-operative condition: 
  
Patients 
number 
Follow up 
Mean or 
median 
SD or 
IQR/1.34 
Reference 
134  
6 months 
84.5  
12.1  
(Ra 2014) 
134  
12 months 
89.8  
9.9  
28  
pre-op  
50.9  
14.2  
(Van de Graaf 2014)  
43  
5 months 
59.8  
20.2  
145  
pre-op  
39.9  
18.1  
(Ebrahimzadeh 2015)  
1411  
pre-op  
53  
17.1  
(Cox 2014)  
1308  
2 years 
85  
13.4  
1307  
6 years 
86  
14.1  
3741  
0: subjects with no knee 
injury  
91  
12.8  
(Anderson 2006)  
4792  
Unknown: Subjects with 
at least one knee 
problem  
(treated or not)  
84  
20.5  
 
In addition, articles (Cox 2014) and (Irrgang 2006) mention an IKDC threshold of 11 points to detect a 
clinically significant change, in a context of pre / postoperative comparison. 

 
 
 
 
 
 
 
 
 
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I.3. RESEARCH HYPOTHESES 
The main objective of this study is to evaluate the performance of the Polylactic Interference Screw for 
ACL reconstruction with hamstring tendons in terms of objective (clinical evaluation) and subjective 
(functional evaluation) IKDC scores. In the one hand, the hypothesis is at least 70% of the patients who will 
undergo ACL reconstruction with PIS will improve their objective IKDC from C or D to A or B (normal or 
almost normal) at 7 months (±1 month) post-surgery visit. In the other hand, our hypothesis is that the 
patients who will undergo ACL reconstruction with PIS will improve their subjective IKDC at least of 11 
points at 7 months (±1 month) post-surgery visit. 
I.4. JUSTIFICATION OF METHODOLOGICAL CHOICES 
After patient information, objective and subjective IKDC scores will be collected before the operation and 7 
months ±1 month after the operation and a clinical examination is scheduled 2 months ± 2 weeks after the 
operation. 
All the examinations carried out are standard examinations, already integrated in the follow-up of the 
patients with lesion of the ACL according to the recommendations of good clinical practice. 
 
The co-primary endpoint includes two main evaluation criteria to conclude on the efficacy of ACL 
reconstruction with PIS. The co-primary endpoint will be evaluated by objective and subjective IKDC 
scores recorded before surgery and at 7 months (±1 month) post-operative follow-up visit. The IKDC scores 
after surgery will be compared to the IKDC scores pre-surgery to determine the efficacy of the 
ligament/graft fixation by the screw. 
I.5. EXPECTED IMPACTS 
The study will confirm the performance and safety of the PIS in anterior cruciate ligament ruptures and its 
acceptable benefit/risk balance.  
 
II. 
OBJECTIVES AND OUTCOMES 
II.1. PRIMARY OBJECTIVE AND CO-PRIMARY ENDPOINT 
The main objective of this study is to evaluate the performance of the Polylactic Interference Screw for 
ACL reconstruction at 7 months (±1 month) based on a co-primary endpoint including two main evaluation 
criteria: 
· 
The objective IKDC score (clinical evaluation) 
· 
The subjective IKDC (functional evaluation) 

 
 
 
 
 
 
 
 
 
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The co-primary endpoint will be recorded at two times:  
· 
Before the operation (up to 4 months before surgery) (V-1) 
· 
7 months after the operation (±1 month) (V3) 
The IKDC scores recorded at V3 will be compared to the scores recorded at V-1. 
 
II.2. SECONDARY OBJECTIVES AND ENDPOINTS 
The secondary objectives of this study are  
· 
To evaluate the safety of the use of these screws by recording all adverse events that occurred 
during the study 
· 
To follow the patient’s recovery through a clinical examination at 2 months post-surgery (±2 
weeks) 
 
III. 
RESEARCH DESIGN 
III.1. 
CLASSIFICATION OF THE STUDY 
This clinical investigation is monocentric (Centre ORTHEO, Orthopaedic and Traumatological Surgery 
Department), prospective, single arm and intra-subject comparative. 
The study is classified as category 3 (non-interventional study) according to the Jardé Law (French Law 
relative to the Clinical Research Involving Human Persons).  
Indeed, according to the terms of the protocol established in collaboration with the stakeholders, this 
research will be carried out on a CE-marked device (CE 0123) and does not involve any risk or constraint 
since all the procedures will be performed and the products used in a usual way, without any additional or 
unusual diagnostic, treatment or monitoring action. 
III.2. 
THE RESEARCH PROJECT AGENDA 
· 
Duration of the inclusion period: 12 months. 
· 
Duration of follow-up per participant: maximum 12 months (at most 4 months before surgery and 8 
months of follow-up). 
· 
Total duration of the research: 24 months. 
 
 

 
 
 
 
 
 
 
 
 
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III.3. 
SUMMARY TABLE OF THE PARTICIPANT FOLLOW-UP 
 
 
Before 
surgery 
V-1 
Surgery 
V0 
At discharge 
V1 
At 2 months 
V2 
At 7 months 
V3 
 
-4 months to 
Day 0 
D0 
D0 
±2 weeks 
±1 month 
Full information and consent 
X 
 
 
 
 
Inclusion / exclusion criteria 
X 
X 
 
 
 
Demographic data 
X 
 
 
 
 
Patient information a 
X 
 
 
 
 
Life habits b 
X 
 
 
 
 
Relevant medical and surgical 
histories 
X 
 
 
 
 
ACL RECONSTRUCTION 
Batch number of PIS used for tibial 
fixation 
 
X 
 
 
 
Batch number of PIS used for 
femoral fixation 
 
X 
 
 
 
Clinical indication 
 
X 
 
 
 
PERFORMANCE 
Visual clinical examinationc 
 
 
 
X 
 
IKDC questionnaire 
- 
Subjective evaluation 
- 
Objective evaluation 
 
X 
X 
 
 
 
 
X d 
 
X 
X 
SAFETY 
AEs 
X<------------------------------------------------------------------------->X 
a. Patient information: height, weight, affected knee 
b. Life habits: smoker, sport activities 
c. Visual clinical evaluation: healing at the surgical site, walking test, quadriceps lock, articular amplitude 
(measured with a goniometer) 
d. Evaluation of 2 items of the IKDC questionnaire at 2 months: Lachmann test and joint effusion items 
III.4. 
INFORMATION OF THE PERSONS CONCERNED 
During pre-inclusion visit, the Investigator (a qualified individual) will ask the participant and/or the legal 
guardians/legal representative to participate in the research project and provide him/her/them with 
information regarding: 
· 
The objective of the study 
· 
The automatic processing of participant-related data that will be collected during the research 
project, and shall also specify the participant’s right to access, object to, or rectify the data. 
The Investigator (a qualified individual) will also ensure that the eligibility criteria are met. If a person 
agrees to participate, he or she will give their consent orally. His or her non-opposition to data use will be 
recorded on a signed form and stored in his or her medical file. The participant may, at any moment, oppose 
the use of his or her data as part of the research. 

 
 
 
 
 
 
 
 
 
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III.5. 
FOLLOW-UP VISITS 
Ø V -1, pre-inclusion visit: -4 months to Day 0 (before surgery) 
o Check of inclusion/exclusion criteria 
o Patient Information: weight, height, affected knee (right, left) 
o Demographic data: Age, sex 
o Life habits: smoker, sport activities 
o Relevant medical and surgical histories 
o IKDC questionnaires (objective and subjective dimension) 
o Signature of the written consent 
 
Ø V 0, inclusion visit: surgery 
o Check of inclusion/exclusion criteria 
o Batch number of the PIS used for femoral fixation 
o Batch number of the PIS used for tibial fixation 
o Clinical indication (Double-Louped SemiTendinosus and Gracilis tendon (DLSTG), 
SemiTendinosus tendon (ST4) or Bone-Patellar Tendon-Bone (BPTB also called Kenneth 
Jones method) 
o AEs report 
 
Ø V 1, follow-up visit: at discharge 
o AEs report 
 
Ø V 2, follow-up visit: at 2 months (±2 weeks) 
o Visual clinical examination: healing, walking test, quadriceps lock and articular amplitude 
o Several items of the objective IKDC questionnaire (Lachmann test and joint effusion items) 
o AEs report 
III.6. 
END OF RESEARCH VISIT 
Ø V 3, follow-up visit: at 7 months (±1 month) 
o IKDC questionnaires (objective and subjective dimension) 
o AEs report 
 

 
 
 
 
 
 
 
 
 
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IV. 
STUDY POPULATION 
IV.1. 
INCLUSION CRITERIA 
1. Acute or chronic ACL deficiency with complete or partial lesion of the anteromedial bundle 
requiring primary reconstruction of the ACL with hamstring tendons  
2. Males or Females aged 18 to 60 years 
3. No history of surgery on the affected knee 
4. Patients not under guardianship or judicial protection 
5. Signature of non opposition form (consent of the patient) 
 
IV.2. 
EXCLUSION CRITERIA 
1. History of ligament, meniscal surgery or fracture on the affected knee  
2. Pregnancy or breastfeeding women 
 
IV.3. 
FEASIBILITY AND RECRUITMENT PROCEDURES  
The study will be conducted at the at the Centre ORTHEO Orthopaedic and Traumatological Surgery 
Department in association with Dr François-Xavier VERDOT. The service already has a systematic and 
standardized follow-up of the patient with an ACL lesion developed according to the recommendations in 
good clinical practice. 
The site is currently doing more than 100 ACL reconstructions a year. The service will recruit a maximum 
of 56 patients. All patients recruited will be patients requiring ACL reconstruction and who will receive the 
Polylactic Interference Screw manufactured by Biomatlante. The indication of treatment (surgical or not) 
will not be influenced by the study and will be performed according to good clinical practice. 
The inclusion of patients is scheduled for a maximum of 12 months. 
Patients fulfilling the study criteria will be offered to participate in the study. Those who accept will be 
assigned an identification number. This number will be re-used on all documents related to the study in 
order to preserve the patient's anonymity on these documents.  
 

 
 
 
 
 
 
 
 
 
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IV.4. 
ACTIONS UPON PATIENT WITHDRAWAL  
If a patient withdraws prematurely from the study, study personnel should make every effort to complete 
the full panel of assessments scheduled until the 7-months visit. The reason for patient withdrawal must be 
documented in the electronic Case Report Form (eCRF). 
Participation of a patient in this clinical study may be discontinued for any of the following reasons: 
· 
The patient withdraws consent or requests discontinuation from the study for any reason; 
· 
Occurrence of any medical condition or circumstance that exposes the patient to substantial risk 
and/or does not allow the patient to adhere to the requirements of the protocol; 
· 
Any SAE, clinically significant adverse event, which indicates to the Investigator that continued 
participation, is not in the best interest of the patient; 
· 
Pregnancy; 
· 
Patient failure to comply with protocol requirements or study-related procedures; or 
· 
Termination of the study by the Sponsor or the regulatory authority.  
In the case of patients lost to follow-up, attempts to contact the patient must be made and documented in the 
patient’s medical records. Withdrawn patients will not be replaced. 
 
V. 
TREATMENT/ STRATEGY(IES)/ PROCEDURE(S) OF THE RESEARCH 
V.1. DESCRIPTION 
OF 
SURGICAL 
TREATMENT 
FOR 
ACL 
RECONSTRUCTION 
(HAS 
RECOMMENDATIONS) 
Intra-articular ligamentoplasty technique: 
Ligamentoplasty is preferentially performed by arthroscopy taking into account the complete assessment of 
the articulation that it allows in the same operating greater rapidity of operative follow-up, decrease in 
morbidity, speed of recovery. 
 
Which transplant? 
· 
No prospective comparative study concludes on the use of the quadricipital tendon or fascia lata. 
· 
Overall subjective and objective results are identical with transplant Bone-Patellar Tendon-Bone 
(BPTB technique also called Kenneth Jones technique) or the transplant using the Double-Louped 
SemiTendinosus and Gracilis tendon (DLSTG technique). 

 
 
 
 
 
 
 
 
 
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· 
The anterior pains (of tendinous or neuropathic origin) and the flessum are more frequent with the 
BPTB than with the DLSTG but the impact on the level of sports recovery is equivalent between 
the two techniques. Previous pain can, however, have a professional impact (an activity requiring 
kneeling). 
 
What fixation? 
Patellar Bone-Tendon Bone (BPTB technique also called Kenneth Jones technique): 
· 
The fixation with a femoral interference screw and a tibial interference screw is the reference 
technique. 
· 
Double fixation to the femur or tibia is useless unless the screw is held poorly interference 
(especially in the tibia). 
· 
The screw can be metallic or bioresorbable. 
· 
The bioresorbable screw has the advantage of facilitating the reading of a possible postoperative 
MRI and possible surgical revision. 
 
Double-Louped SemiTendinous and Gracilis tendon (DLSTG technique): 
· 
In the femur, it can use an extra-anatomic system, an interference screw or any other intraductal 
system. To date, no study recommends a double femoral fixation. 
· 
In the tibia, the traction is in the axis of the transplant. This can lead to propose, especially when the 
bone behaviour is poor, a double fixation or strengthened. 
 
Lateral tenodesis: 
· 
Regardless of age, isolated lateral tenodesis is not recommended. 
· 
There is no indication to perform systematic associated lateral tenodesis, in front of chronic anterior 
laxity. 
· 
Lateral tenodesis associated with intra-articular reconstruction cannot be considered only in the 
context of an overall previous laxity. 
 

 
 
 
 
 
 
 
 
 
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V.2. DESCRIPTION OF THE PRODUCT 
The Polylactic Interference Screw (PIS) manufactured by Biomatlante is a sterile, resorbable and synthetic 
implant made up of 100% polymer. Indeed, it consists of a polymer: poly (L-lactide-co-D, L-lactide) 
(PLDLLA). The Polylactic Interference Screw is in the form of a cannulated screw: 
 
 
Figure 1: Polylactic Interference Screw 
 
The Polylactic Interference Screws are available in different diameters (from 7 to 12 mm), and several 
different lengths depending on the diameters (from 20 to 35 mm). Different diameters and lengths of 
implants are available to allow adaptation to the bone site but also to the patient's anatomy. 
The design is suitable for easy installation, without tissue damage. 
The Polylactic Interference Screw is intended to be fully absorbed by the body during the process of bone 
healing. 
V.3. INTENDED USE 
The Polylactic Interference Screw is intended to be used for knee ligament reconstructions. 
The claimed performance for the Polylactic Interference Screw is as follows: fixation of the ligament/graft 
within the bone tunnel until bone consolidation is complete. 
 
V.4. SURGICAL INDICATION 
The Polylactic Interference Screw is indicated for torn ligaments in the knee.  
The Polylactic Interference Screw is reserved exclusively for adults. The material has not been tested on 
pregnant or breastfeeding women. 
 

 
 
 
 
 
 
 
 
 
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V.5. CHOICE OF TREATMENT IN THE STUDY 
Recruited patients will have an indication of ACL reconstruction with a tendon graft from hamstring 
muscles:  
- 
DLSTG (Double-Louped SemiTendinosus and Gracilis) technique: use of tendon grafts from the 
Double-Louped SemiTendinosus and Gracilis muscles 
- 
ST4 (SemiTendinous) technique: use of a tendon graft only from the SemiTendinosus muscle. 
In the femur and in the tibia, the fixation will be assured by the Polylactic Interference Screw. The 
indication of treatment (surgical or otherwise) after ACL injury will not be influenced by the study and will 
be performed according to good clinical practice. 
Patients for whom a patellar tendon (BPTB technique also called Kenneth Jones technique) is advised by 
the surgeon according to good clinical practice will not be included. 
During this study, the investigators' practices will not be modified. For each type of surgery, the surgeon 
will perform all his acts in accordance with his current practice, without adding any additional procedure.  
The Polylactic Interference Screw should be handled in accordance with the manufacturer's 
recommendation using sterile instruments.  
V.6. CONTRAINDICATIONS 
· 
Acute infections 
· 
Known allergies to the material (if an allergy of any type is suspected, the appropriate examinations 
must be carried out beforehand) 
· 
Fever and/or local inflammation 
· 
Mediocre or insufficient bone quality (especially in the event of tumours and severe osteoporosis). 
· 
Limited blood flow at the graft site (necrosis, prior infections) 
V.7. AUTHORIZED OF FORBIDDEN TREATMENTS AND PROCEDURES 
No prior or concomitant medication will be prohibited. 
 
VI. 
STUDY ASSESSMENT AND PROCEDURES 
VI.1. 
MAIN EVALUATION CRITERION 
For assessment of PIS performance in ACL reconstruction, the investigator will evaluate the objective 
IKDC score and the patient will evaluate the subjective IKDC score: 
· 
Before the operation (up to 4 months before surgery) 
· 
7 months after the operation (±1 month) 

 
 
 
 
 
 
 
 
 
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The objective IKDC exam is a classic manual examination of the surgeon during the diagnosis and follow-
up of the patient and does not involve any risk for the patient. Four level are used in objective IKDC 
evaluation coded from A to D (A: Normal, B: Almost normal, C: Abnormal and D: Very abnormal). The 
first three item groups (joint effusion, loss of passive mobility and ligament assessment) will be used to 
determine the objective IKDC score. The item group with the lowest level determines the final evaluation 
for the objective IKDC evaluation. The item groups from 4 to 7 are not required for the determination of the 
objective IKDC score; the completion of these item groups is optional. In this study, only the first three 
items groups will be completed. 
The subjective IKDC questionnaire provides an overall functional score. The questionnaire looks at 3 
categories: symptoms, sports activity, and knee function. The symptoms subscale helps to evaluate things 
such as pain, stiffness, swelling and giving-way of the knee. Scores are obtained by summing the individual 
items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is 
interpreted as a measure of function with higher scores representing higher levels of function. 
VI.2. 
SECONDARY EVALUATION CRITERIA 
Safety assessment of PIS in ACL reconstruction, the investigator will report all Adverse Events (AEs) 
 
The clinical examination performed during the 2-months visit allows the surgeon to follow the patient's 
recovery. The parameters collected during this visit are as follows: 
· 
Visual clinical examination: 
- 
Healing at the surgical site: total healing, partial healing and no healing. 
- 
Walking test: the patient always uses these crutches (yes/no). 
- 
Quadriceps lock: when the leg is extended, if the kneecap rises, the patient has locked his 
quadriceps properly and we have a recovery of the quadriceps function. The answer will be 
yes/no. 
- 
Articular amplitude: the test is carried out using a goniometer to measure the flexion angle and 
the extension angle. The values in degrees will be recorded both in flexion and extension. 
 
· 
Objective IKDC items: 
- 
Lachman test: the Lachman test will be performed manually. This test is a passive accessory 
movement test of the knee performed to identify the integrity of the anterior cruciate ligament 
(ACL) and is designed to assess single and sagittal plane instability. 
- 
Joint effusion: the joint effusion is determined by palpation of the knee.  
 

 
 
 
 
 
 
 
 
 
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VI.3. 
MANAGEMENT OF ADVERSE EVENTS 
The investigator records the adverse events or an abnormal analysis result defined in the protocol as 
determinants for the safety assessment, keeps a documentary record and notifies the sponsor. 
The investigator informs the sponsor of all adverse events that occurred in the participants. 
 
VI.3.1. DEFINITION OF ADVERSE EVENTS 
An adverse event is defined as any untoward medical occurrence in a clinical investigation patient 
administered a medical device, which does not necessarily have a causal relationship with this device. An 
adverse event can therefore be any unfavorable and/or unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an investigational product, whether or 
not related to the investigational product. All adverse events, including observed or volunteered problems, 
complaints, or symptoms, are to be recorded on the eCRF. 
Adverse events will be monitored and documented from the time of informed consent to the end of study 
participation. Patients should be instructed to report any adverse event that they experience to the 
Investigator. Beginning with the signing of informed consent, investigators should make an assessment for 
adverse events at each visit and record the event on the adverse event section of the eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and symptoms 
should be identified by the Investigator and recorded on the eCRF. However, if an observed or reported sign 
or symptom is not considered a component of a specific disease or syndrome by the Investigator, it should 
be recorded as a separate adverse event on the eCRF. Additionally, the condition that led to a medical or 
surgical procedure (e.g., surgery, endoscopy, transfusion) should be recorded as an adverse event. 
Any medical condition already present at the time of screening should not be reported as an adverse event 
unless the medical condition or signs or symptoms present at baseline changes in severity or seriousness at 
any time during the study. In this case, it should be reported as an adverse event. 
 
 
VI.3.2. DEFINITION OF SERIOUS ADVERSE EVENTS 
An adverse event or adverse reaction is considered serious if, in the view of either the Investigator or 
Sponsor, it results in any of the following outcomes: 
· 
Death: AE causes or contributes to the death; 
· 
A life-threatening adverse event: AE places the subject at immediate risk of death; it does not refer 
to AE which hypothetically might have caused death if it were more severe; 

 
 
 
 
 
 
 
 
 
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· 
Requires hospitalization or prolongation of existing hospitalizations: AE requires at least an 
overnight admission or prolongs a hospitalization beyond the expected length of stay. Hospital 
admissions for surgery planned before study entry, for social reasons, for any elective surgery (i.e. 
plastic surgery) or for normal disease management (including treatment adjustment) are NOT to be 
considered as SAE according to this criterion; 
· 
A persistent or significant disability/incapacity or substantial disruption of the ability to conduct 
normal life functions; 
· 
A congenital anomaly/birth defect;  
· 
An important medical event: AE that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed above. 
The Investigator must continue to follow the patient until the SAE has subsided or until the condition 
becomes chronic in nature, stabilizes (in the case of persistent impairment), or the patient dies. 
 
VI.3.3. CLASSIFICATION OF AN ADVERSE EVENT 
VI.3.3.1. 
Severity of event 
The severity of AEs must be assessed by the Investigator according to the following definitions. The term 
“severity” is used to describe the intensity of a specific event. This has to be distinguished from the term 
“serious”. 
· 
Mild: Events require minimal or no treatment and do not interfere with the participant’s daily 
activities 
· 
Moderate: Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
· 
Severe: Events interrupt a participant’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating.  Of note, 
the term “severe” does not necessarily equate to “serious”. 
VI.3.3.2. 
Relationship to study product 
The clinician must always determine the relationship between all adverse events and the investigated 
medical device by the examination and evaluation of the participant on the basis of temporal relationship 
between the AE and application of the device and his/her clinical judgment. In a clinical trial, the 
investigated medical device must always be suspected. The degree of certainty about causality will be 
graded using the categories below: 

 
 
 
 
 
 
 
 
 
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· 
Definitely Related: There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study intervention (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
· 
Probably Related: There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
· 
Potentially Related: There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
· 
Unlikely to be related: A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the study intervention) 
and in which other drugs or chemicals or underlying disease provides plausible explanations (e.g., 
the participant’s clinical condition, other concomitant treatments). 
· 
Not Related: The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an alternative, 
definitive etiology documented by the clinician 
 
VI.3.3.3. 
Expected adverse events 
The most frequent adverse events expected from Polylactic Interference Screw observed in patients are: 
· 
Postoperative infection 
· 
Irritation 
· 
Allergy 
· 
Reduced patient mobility 
· 
Pain 
· 
Fever 
· 
Inflammatory reaction 

 
 
 
 
 
 
 
 
 
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Certain adverse events can be treated with medicines or may require additional surgery. 
VI.3.4. ADVERSE EVENTS REPORTING 
Complete and accurate data on all AEs experienced for the duration of the reporting period, will be reported 
in the eCRF. 
It is important that each AE report includes a description of the event, whether it is considered serious, its 
duration (onset and resolution dates), its severity, its relationship to the investigational product, any other 
potential causality factors, any treatment given or other action taken and its outcome. 
As defined in Article R5212-17 of the French Public Health Code, all incident or risk of incident resulting 
from the use of a medical device brought to the investigator’s attention will be the subject of a spontaneous 
report from the investigator to the local vigilance correspondent on whom he depends or, failing that, to the 
French National Agency for the Safety of Health Products (Agence Nationale de Sécurité et du 
Médicament : ANSM) in accordance with the usual procedures in force.  
 
These declarations should be addressed at:  
 
Direction de la surveillance – Plateforme de réception et d’orientation des signalements 
E-mail: materiovigilance@ansm.sante.fr 
Fax: 01.55.87.37.01 
All AEs occurring from the time of informed consent until end of study participation must also be reported 
to the sponsor.  
All AEs that the Investigator considers related to the medical device occurring after the end of study 
participation must be reported to the sponsor.  
 
To report the AE, the AE form can be filled. When the form is completed, signed and dated, it must be sent 
to the sponsor, specifically to the vigilance contact:  
Vigilance contact : 
Nancy TRICHEREAU 
Quality Assurance Manager 
E-mail: materiovigilance@biomatlante.com 
Phone: 06.21.90.58.43 
Immediately after receiving the follow-up information, the Investigator must update the AE form and 
submit any supporting documentation (e.g., patient discharge summary or autopsy reports) to the sponsor. 

 
 
 
 
 
 
 
 
 
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For any research involving the human, where an unexpected serious adverse reaction or a new fact relevant 
to the research or product under investigation is likely to prejudice to the safety of the appropriate persons, 
the proponent and the investigator shall take appropriate urgent safety measures. 
VI.3.5. NEW FACTS REPORTING 
A new fact is defined as any new safety data which may lead to a reassessment of the relationship between 
the benefits and risks balance of the research or the product being investigated, changes in the use of the 
product, the conduct of the research or documents relating to the search, or to suspend or interrupt or 
modify the protocol of the search or similar searches. (R.1123-46 of the French Public Health Code). 
In the case of a new medical fact, the Sponsor, will be responsible for reporting new facts to the authorities 
in accordance with national regulations, as follows: 
· 
Inform without delay the ANSM about the new medical fact, at the following email address: aec-
essaiscliniques@ansm.sante.fr with the following subject: Fait nouveau / trial number/ international 
non-proprietary name (INN) or substance code and including: 
- 
ID-RCB N°, 
- 
Title of the study protocol, 
- 
Protocol code number, 
- 
Summary of the new fact and urgent safety measures implemented if necessary, 
- 
All relevant information for the evaluation of the new fact. 
· 
Inform without delay the director of the Agence Régionale de Santé (ARS; regional health agency) 
and the Ethics Committee (CPP). 
Any follow-up information with regards to the new safety medical fact will be reported to the regulatory 
authorities within 8 calendar days, and details regarding the urgent safety measures set up will be sent 
within 15 days to the regulatory authorities. 
 
VII. STATISTICAL ASPECTS 
VII.1. 
SAMPLE SIZE DETERMINATION 
The sample size required for the study was determined in order to obtain sufficient final statistical power 
considering the 2 main criteria (co-primary endpoint). The statistical power used to determine the sample 
size required for each of the 2 main criteria is 90% to obtain a final statistical power of at least 80%. 
 
 
 
 

 
 
 
 
 
 
 
 
 
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Subjective IKDC:  
The minimum relevant difference expected in the change at 7 months on the functional IKDC score is 11 
points and the standard deviation expected in the IKDC score at pre-surgery and at 7 months is 13 points. A 
total of 32 evaluable patients will be necessary to ensure a 90% power to detect a significant difference in 
the change at 7 months for two-sided test at the 5% level using paired Student t test. 
 
Objective IKDC:  
It is expected that 96% of patient will have modalities C or D before surgery [5]. Based on the investigator's 
experience, the proportion of total expected to shift from an IKDC modalities C or D to modalities A or B is 
70% and proportion of total expected to shift from an IKDC modalities A or B to modalities C or D is 1%. 
A total of 11 evaluable patients will be necessary to ensure a 90% power to detect a significant difference 
for two-sided test at the 5% level using McNemar test. 
 
In order to ensure sufficient statistical power for both comparisons, the larger of the two required sample 
size is planned to be included, i.e. 32 patients. 
 
However, to increase the estimate precision of the co-primary endpoint, 50 completed patients will be 
targeted. With 50 patients, a precision around 13% can be achieved for the objective IKDC score and 3.6 
points for the subjective IKDC score. This sample size will provide a final statistical power for primary 
objective of 97%. 
 
Accounting for a maximum of 10% dropouts or missing data, 56 patients should be recruited in the study. 
VII.2. 
ANALYSIS SETS 
Four populations will be defined: 
· 
Screened population will include all patients entering the study,  
· 
Safety Set (SS) population will include all patients who received the surgical intervention, 
· 
Full Analysis Set (FAS) population will be defined by all patient who received the PIS product and 
in whom at least one efficacy information has been collected after the application of the PIS, 
· 
Per-Protocol (PP) efficacy population will include all patients in FAS population without any major 
protocol deviation. 
Remark: according to the ICH E9 recommendations, this subset of patients corresponds to a subset of the 
full “intention-to-treat” analysis set, being the Full Analysis Set (FAS). 

 
 
 
 
 
 
 
 
 
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VII.3. 
MISSING VALUES AND DROP-OUT 
For the primary analysis (FAS analysis), in the case of a patient with missing data, the corresponding data 
will not be replaced. 
For sensitivity analyses, some of the missing data may be replaced. It will be performed according to the 
following scenarios: 
· 
Best-worst scenario: the missing data on the pre-surgery objective IKDC score will be considered 
with an objective IKDC score to A and missing data on the 7-months objective IKDC score will be 
considered with an objective IKDC score to D. 
· 
Worst-best scenario: the missing data on the pre-surgery objective IKDC score will be considered 
with an objective IKDC score to D and missing data on the 7-month objective IKDC score will be 
considered with an objective IKDC score to A. 
· 
Last Observation Carry Forward (LOCF) method: the missing data on the 7-months subjective 
IKDC will be replaced using LOCF method. 
No other missing data will be replaced. 
VII.4. 
STATISTICAL ANALYSIS 
VII.4.1. GENERAL CONSIDERATION 
A Statistical Analysis Plan (SAP) will be written by the biostatistician detailing the statistical analysis. This 
document will be approved and signed by the Sponsor and the Coordinating Investigator before the first 
database lock. 
The statistical analysis will be performed on SAS® version 9.4 or later (or equivalent statistical software). 
Ø Descriptive statistics 
Quantitative variables will be described by the number of values entered, the number of missing data, the 
mean, the standard deviation, the 95% CIs for the means, the median, the 1st and 3rd quartiles, the minimum 
and maximum. 
Qualitative variables will be described by the number of data filled in, the number of missing data, the 
frequency and the percentage of each modality. The 95% CIs of the percentages will be performed using 
exact confidence limits method. 
All variable in the database will be described using descriptive statistics and all individual data will be 
presented in listings. 
 
 

 
 
 
 
 
 
 
 
 
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Ø Inferential test 
All tests will be two-sided and the type I error (α) will be set at 5%. 
Quantitative score at 7-months visit will be compared to the score before surgery using paired Student t test 
or Wilcoxon test (depend of normality assumption). 
Qualitative score at 7-months visit will be compared to the score before surgery using exact McNemar test. 
One interim analysis and no sub-group analysis will be planned. 
 
Ø Pre-analysis review of patient data  
Following the ICH guideline E9, a data review meeting will be held before the final database locking. The 
following items will be discussed:  
· 
By-patient, list of protocol violations and other issues with the data, and definition of the analysis 
sets,  
· 
Need for amendment to the SAP, based on newly gained research information and on the 
examination of the data.  
If required, the SAP will be amended. Data discrepancies detected at the pre-analysis data review meeting 
will be resolved. Subsequently, the database will be locked, and the analyses will be performed. 
 
Ø Protocol deviations  
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or manufacturer recommendation requirements. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. It is the 
responsibility of the site investigator to use continuous vigilance to identify deviations. All deviations must 
be reported in study source documents. 
All protocol deviations will be listed before the data review meeting and reviewed during this meeting and 
classified as “minor” or “major".  
Number and frequency of patients with protocol deviations will be tabulated. 
Patients presenting major deviation will be excluded from the PP efficacy population and therefore will not 
be taken into account on the primary efficacy analysis in the PP population. 
 
 

 
 
 
 
 
 
 
 
 
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VII.4.2. ANALYSIS OF THE CO-PRIMARY EFFICACY ENDPOINT 
According to the Food and Drug Administration (FDA) guidance for industry – Multiple endpoints in 
clinical trials and European Medicines Agency (EMA) Guideline on multiplicity issues in clinical trials, for 
conclude that the PIS is effective, it will be necessary to demonstrate an effect on each of the primary 
endpoints. However, there is only one result that is considered a study success, namely, that all of the 
separate endpoints are statistically significant. Testing all of the individual endpoints at the 0.05 level does 
not cause inflation of the Type I error rate; rather, the impact of co-primary endpoint testing is to increase 
the type II error rate. 
The co-primary endpoint analysis will be performed on FAS population. 
The scores recorded at 7 months (±1 month) after surgery will be compared to the scores recorded before 
surgery. The intra-subject comparison will be the main judgement criteria of success. 
The objective IKDC score will be dichotomised by combining modalities A and B and modalities C and D.  
The objective IKDC score at 7-months visit will be compared to the objective IKDC score before surgery 
using exact McNemar test. 
The subjective IKDC score at 7-months visit will be compared to the subjective IKDC score before surgery 
using paired Student test or Wilcoxon test (depend of normality assumption). 
Sensitivity analyses using different analyses sets and missing data handling as described above will be 
performed as described in section “Missing values / dropouts”. The PP analysis will be considered as 
confirmatory analysis. 
 
VII.4.3. ANALYSIS OF THE SECONDARY EFFICACY ENDPOINT 
The visual clinical examination and the record of specific IKDC items performed during the 2-months visit 
will be summarized using descriptive statistics on the FAS population. 
 
VII.4.4. SAFETY ANALYSIS 
The safety analysis will be performed on SS population. 
Safety endpoints will be AEs and SAEs all through the study.  
AEs will be coded using last version available of the Medical Dictionary for Regulatory Activities 
dictionary (MedDRA). AEs will be classified according to period of occurrence: pre-treatment AEs and 
Treatment-Emergent AEs.  
· 
Pre-treatment AEs are defined as adverse events occurring before the introduction of the 
investigational product.  

 
 
 
 
 
 
 
 
 
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· 
Treatment-Emergent AEs (TEAEs) are defined as an adverse who that emerges after introduction of 
the investigational product having been absent pre-treatment, or worsens relative to the pre-
treatment state. 
AE reporting will focus on TEAEs. TEAEs will be summarized and detailed using descriptive statistics by:  
· 
seriousness,  
· 
intensity,  
· 
action taken with investigational product,  
· 
other action taken,  
· 
relationship to study treatment, 
· 
severity according to the relationship.  
The number and frequency of patients with each TEAE will be displayed by System Organ Class and 
Preferred Term according to Medical Dictionary for Regulatory Activities (MedDRA) classification. 
All SAEs will be listed separately with the same information that the TEAE. 
 
VII.4.5. BASELINE DESCRIPTIVE STATISTICS 
The baseline value will be defined by the last measured value before the ACL surgery. 
Descriptive statistics of demographics and other baseline characteristics will be presented on the FAS 
population. 
Medical history will be summarized for all included patients on the FAS population. Frequency of 
pathologies will be summarized using descriptive statistics. Frequency will be given by system organ class 
and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA). 
Prior and concomitant medications will be summarized for all included patients on the FAS population. 
Prior and concomitant medications coded using the ATC classification system will be tabulated by 
anatomical main group, therapeutic/pharmacological subgroup and by chemical substance. Prior 
medications will be defined as medications used by subjects in the 3 months prior to screening visit and 
stopped before surgery. 
VII.4.6. PLANNED INTERIM ANALYSES 
One interim analysis is planned in this study protocol during the first quarter of 2020. 
This analysis will be carried out using only descriptive statistics. No p-value will be generated in order to 
prevent the alpha inflation for the final analysis. 
VII.4.7. SUB-GROUP ANALYSES 
No sub-group analysis is planned. 

 
 
 
 
 
 
 
 
 
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VII.4.8. TABULATION OF INDIVIDUAL PATIENT DATA 
All individual data will be presented in the listing table in accordance with the guidance ICH E3. 
 
VIII. 
RIGHTS OF ACCESS TO DATA AND SOURCE DOCUMENTS 
 
BIOMATLANTE, sponsor of the research, is identified as the data processing controller. As a result, it 
must be in compliance and ensure that the data will be processed by the various research actors, in 
accordance with Law 78-17 of 6th January 1978 amended by Law 2014-344 of 17th March 2017, known as 
“Informatique et Libertés”, and the European Regulation 2016/679 of 27th April 2016 (known as “GDPR”). 
VIII.1. 
ACCESS TO DATA 
Agreement to participate in the protocol means that the individuals carrying out the research will make 
documents and individual data that are strictly necessary to follow-up, quality control and audit available to 
the individuals who have a right to access these documents in accordance with applicable legal and 
regulatory provisions. 
VIII.2. 
SOURCE DATA 
This includes all information contained in the original documents, or in authenticated copies of these 
documents, relating to clinical examinations, findings or other activities carried out as part of the research 
and necessary to the reconstitution and evaluation of the research. The documents in which source data are 
recorded are called source documents.  
The source document to be used will be: 
· 
Medical patient file 
· 
Patient questionnaires 
VIII.3. 
DATA CONFIDENTIALITY 
In accordance with applicable legal provisions, individuals who have direct access to source data take all 
the necessary precautions to ensure the confidentiality of information relating to research, participants and 
particularly their identity, as well as the results obtained. These individuals, like the investigator and the 
person who performs data monitoring, are subject to the conditions of professional secrecy. 
 
During the research project or at the end of it, the collected data on participants and data transmitted to the 
sponsor by the investigator (or any other involved specialists) will be codified. The data must not, under any 
circumstances, clearly indicate the names of the participants or their address. 
 

 
 
 
 
 
 
 
 
 
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Only the first letter of the name and surname of the subject will be recorded, together with a research-
specific coded number indicating the order of inclusion of the subjects for each center. 
The sponsor will ensure that each participant of the research project will be informed about access to data 
relating to him or her and strictly necessary for quality control. 
 
VIII.4. PSEUDONYMIZATION PROCEDURE 
In the context of this study, the personal data of patients will be processed in order to meet the research 
objectives.  
For this purpose, patient’s medical data will be transmitted to the sponsor. For each patient, these data will 
be identified by the number attributed to the research center and the identification number of the patient.  
 
The number attributed to the research center is attributed as follows:  
Clinical center N°01 : Centre ORTHEO, Orthopedic Surgery Department - Dr François-Xavier VERDOT 
The patient identification number is attributed as follows:  
- 
Number corresponding to the order of inclusion in the research center 
- 
First letter of the patient’s first name 
- 
First letter of the patient’s name 
 
Center N°: ǁ_0 1_ǁ 
Patient inlcusionN°: ǁ_0_ǁ_1_ǁ_X_ǁ_X_ǁ 
                                Inclusion N° 
 
Investigator : _________________________ 
 
Only the investigator, its collaborators and the person responsible for the quality control of the data will 
have access to directly identifying data (name, date of birth, etc) via the correspondence table.  
 
 

 
 
 
 
 
 
 
 
 
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IX. 
QUALITY CONTROL AND QUALITY ASSURANCE 
IX.1. 
GUIDELINES FOR COLLECTING DATA 
All the information required by the protocol must be recorded in case report forms and an explanation must 
be provided for any missing data.  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.  
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data.   
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study. Data recorded in the electronic case report form 
derived from source documents should be consistent with the data recorded on the source documents. 
Clinical data will be entered directly from the source documents. 
 
IX.2. 
RESEARCH FOLLOW-UP 
The Clinical Research Associate (CRA) will ensure research follow-up and will be responsible, under the 
Coordinating Investigator, for: 
· 
Logistics and the monitoring of research, 
· 
Reporting on the study’s progress, 
· 
Verifying that the case report form is updated (request for additional information, 
corrections, etc.), 
· 
Sending samples. 
The CRA will work in accordance with standard operating procedures, in collaboration with the research 
associate delegated by the sponsor. 
IX.3. 
QUALITY ASSURANCE AND QUALITY CONTROL 
A CRA will visit each center, during the implementation of the research, once or several times during the 
course of the research project, according to the monitoring plan defined for the research and the frequency 
of inclusions. The elements to be reviewed during these visits are defined by the monitoring plan. All visits 
will be subject to a written monitoring report. The sponsor will be in charge of the quality survey of the 
study. 

 
 
 
 
 
 
 
 
 
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Following written monitoring plan, the clinical research associate will verify that the clinical trial is 
conducted and data are generated, documented (recorded), and reported in compliance with the protocol, 
International Conference on Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory 
requirements (e.g., Good Manufacturing Practices).  
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 
IX.4. 
DATA MANAGEMENT 
IX.4.1. DATA HANDLING 
Data will be recorded at the site on eCRFs and reviewed by the CRA during monitoring visits. The CRAs 
will verify data recorded in the electronic data capture (EDC) system with source documents. All 
corrections or changes made to any study data must be appropriately tracked in an audit trail in the EDC 
system. An eCRF will be considered complete when all missing, incorrect, and/or inconsistent data has 
been accounted for. 
 
IX.4.2. COMPUTER SYSTEMS 
Data will be processed using a validated computer system conforming to regulatory requirements. 
 
IX.4.3. DATA ENTRY 
Data must be recorded using the EDC system as the study is in progress. All site personnel must log into the 
system using their secure user name and password in order to enter, review, or correct study data. These 
procedures must comply with Title 21 of the Code of Federal Regulations (CFR) Part 11 and other 
appropriate international regulations. All passwords will be strictly confidential. 
 
IX.4.4. MEDICAL INFORMATION CODING 
For medical information, the latest version at the time of study start of the Medical Dictionary for 
Regulatory Activities (MedDRA) for medical history and adverse events will be used. 
 
IX.4.5. DATA VALIDATION 
Validation checks programmed within the EDC system, as well as supplemental validation performed via 
review of the downloaded data, will be applied to the data in order to ensure accurate, consistent, and 
reliable data. Data identified as erroneous, or data that are missing, will be referred to the investigative site 
for resolution through data queries. 

 
 
 
 
 
 
 
 
 
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The eCRFs panel for each patient will be electronically signed by the Investigator. 
 
IX.5. 
PROTOCOL DEVIATION 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or manufacturer recommendation requirements. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. It is the 
responsibility of the site investigator to use continuous vigilance to identify deviations. All deviations must 
be reported in study source documents. 
Examples of protocol deviations are presented below (non-exhaustive list):  
· 
The screw has not been installed,  
· 
Violation of inclusion/non-inclusion criteria,  
· 
Post-inclusion protocol violation, 
· 
Non compliance with visit scheduled 
 
All protocol deviation will be listed before the data review meeting and reviewed during this meeting and 
classified as “minor” or “major".  
Number and frequency of patients with protocol deviations will be tabulated. 
IX.6. 
AUDIT AND INSPECTION 
Individuals appointed by the sponsor and independent of those conducting the study may carry out audits at 
any moment. The audit is designed to check the safety of the participants and the respect of their rights, 
compliance with applicable regulations and data reliability. 
An inspection may also be undertaken by a competent authority (ANSM in France or EMA within the 
framework of a European study, for example). 
The audit, as well as the inspection, may be applied to any stage of the research, from protocol development 
to the publication of results and the classification of data used or produced as part of the research project. 
The investigators shall comply with the sponsor’s requirements regarding the audit and the competent 
authority’s inspection of the research. 
 
 

 
 
 
 
 
 
 
 
 
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X. 
 ETHICAL AND REGULATORY CONSIDERATIONS 
X.1. COMPLIANCE WITH REFERENCE TEXTS 
The sponsor and the person(s) who directs(s) and supervise(s) the research commit themselves to ensure 
that this research is carried out in accordance with the law no. 2012-300 of 5 March 2012 on research 
involving the human person and the Declaration of Helsinki (which can be found in full at 
http://www.wma.net/en/30publications/10policies/b3/). 
This research project will receive the positive endorsement of the CPP (Committee for the Protection of 
Persons – French equivalent of an Ethical Committee) and will be reported to the ANSM (the French 
National Agency for the Safety of Health Products).The data recorded during this research are the subject of 
a computerised processing at ATLANSTAT in accordance with the law no. 78-17 of 6 January 1978 on 
data processing, files and freedom as amended by Law 2004-801 of 6 August 2004. 
This research project falls within the framework of the “Reference methodology” (MR-003). The sponsor 
signed a commitment of compliance with this “Reference methodology”. 
This research has been registered on the site http://clinicaltrials.gov/. 
 
X.2. CHANGES TO THE PROTOCOL  
Any substantial change, i.e. any change that is likely to have a significant impact on the protection of 
persons, on the conditions of validity and on the results of the research, on the quality and safety of the 
products tested, on the interpretation of scientific documents that support the conduct of the research or the 
way in which the research is conducted, is subject to a written amendment submitted to the sponsor. The 
latter must obtain, prior to its implementation, a favourable opinion from the CPP.  
 
Non-substantial changes, i.e, those that do not have a significant impact on any aspect of the research, are 
communicated to the CPP for information. 
 
All changes are validated by the sponsor, and by all research stakeholders involved in the change, before 
submission to the CPP. This validation may require the meeting of all committees formed for the research. 
 
All changes to the protocol must be made known to all persons carrying out the research, who undertake to 
respect its contents. 
 

 
 
 
 
 
 
 
 
 
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XI. 
 PRESERVATION OF RESEARCH DOCUMENTS AND DATA 
The duration of the archiving period is defined by the sponsor according to the applicable procedures and 
regulations.  
The patient data will be kept up to 2 years after the last publication of the research results, or, in absence of 
publication, until the final report of the research is written.  
In accordance with the decree of 11th August 2008 fixing the period of storage by the sponsor and the 
investigator of documents and data relating to biomedical research other than that relating to medicinal 
products for human use, they will then be archived for a minimum period of 15 years.  
 
Data processing operations of the investigator and other professionals involved in the conduct of the 
research may not be stored for more than 5 years after the end of the last research in which the person 
participated. They will be then archived for a minimum period of 15 years.  
 
XII. 
RULES FOR PUBLICATION 
XII.1. 
SCIENTIFIC COMMUNICATIONS 
The analysis of data provided by the centre will be carried out by ATLANSTAT. The analysis will result in 
a written report, submitted to the sponsor. This report will allow for the preparation of one or more 
publication(s). 
Any written or oral communication of the results of the research project must receive prior approval of the 
investigator and, if applicable, of any committee set up for the research project. 
The publication of the main results will mention the name of the Sponsor, of all the people who included or 
followed-up research participants, of methodologists, biostatisticians and data managers who participated in 
the research, of members of the committee(s) set up for the research project. The international rules for 
writing and publishing shall be taken into account (IMCJE’s Uniform Requirements for Manuscripts, April 
2010). 
The primary purpose of the sponsor is the use of these data for regulatory purposes. 
 
XII.2. 
COMMUNICATION OF RESULTS TO PATIENTS 
Upon their request, participants will be informed of the overall results of the research projects explained in 
the patient information.  

 
 
 
 
 
 
 
 
 
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XII.3. 
TRANSFER OF DATA 
ATLANSTAT will ensure data management. The conditions for transferring all or part of the research 
database will be decided by the sponsor and be subject to a written agreement. The data will be transferred 
in a pseudonymized form, the study participant number will be used to identify the patient. Data transfer 
will be encrypted and no data transfer is planned outside the European Union. 

 
 
 
 
 
 
 
 
 
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XIII. 
BIBLIOGRAPHIC REFERENCES 
 
1. Recommandation de bonne pratique/Critères de suivi en rééducation et d'orientation en ambulatoire ou 
en soins de suite ou de réadaptation après ligamentoplastie du croisé antérieur du genou/Avr. 2008 
2. Haute Autorité de Santé, Recommandations professionnelles 2008 : prise en charge thérapeutique des 
lésions méniscales et des lésions isolées du ligament croisé antérieur du genou chez l'adulte 
3. Uzumcugil, O., et al., Effect of PEEK polymer on tunnel widening after hamstring ACL reconstruction. 
Orthopedics, 2012. 35(5): p. e654-9.  
4. Chaory K. and Poireaudeau S. Les grilles d’évaluation dans la ligamentoplastie du LCA. Rating scores 
for ACL reconstruction. Annales de Réadaptation et de Médecine Physique. 2004. (47) 309-316. 
5. Lutz C., et al., Pain after out-patient vs. in-patient ACL reconstruction: French prospective study of 1076 
patients, Orthop Traumatol Surg Res, 2016. 102(8S) S265-S270. 
 
References specific to the IKDC score 
 
Anderson, Allen F., James J. Irrgang, Mininder S. Kocher, Barton J. Mann, John J. Harrast, et  
International Knee Documentation Committee  
« The International Knee Documentation Committee Subjective Knee Evaluation Form: Normative Data ». 
The American Journal of Sports Medicine 34 (1). 2006. (janvier): 128̻135.  
  
Cox, Charles L., Laura J. Huston, Warren R. Dunn, Emily K. Reinke, Samuel K. Nwosu, Richard D.  
Parker, Rick W. Wright, et al.  
« Are Articular Cartilage Lesions and Meniscus Tears Predictive of IKDC, KOOS, and Marx Activity Level 
Outcomes after ACL Reconstruction? A 6-Year Multicenter Cohort Study ». The American journal of 
sports medicine 42 (5). 2014. (mai): 1058̻1067.  
  
Ebrahimzadeh, Mohammad Hosein, Hadi Makhmalbaf, Farideh Golhasani-Keshtan, Shadi Rabani, et Ali 
Birjandinejad  
« The International Knee Documentation Committee (IKDC) Subjective Short Form: A Validity and 
Reliability Study ». Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA 23 
(11). 2015. (novembre): 3163̻3167.  
  
van de Graaf, CIStor A., Nienke Wolterbeek, Vanessa A. B. Scholtes, Eduard L. A. R. Mutsaerts, et Rudolf 
W. Poolman  
« Reliability and Validity of the IKDC, KOOS, and WOMAC for Patients With Meniscal Injuries ». The 
American Journal of Sports Medicine 42 (6). 2014. (juin): 1408̻1416.  
  
Irrgang, James J., Allen F. Anderson, Arthur L. Boland, Christopher D. Harner, Philippe Neyret,  
John C. Richmond, K. Donald Shelbourne, et International Knee Documentation Committee « 
Responsiveness of the International Knee Documentation Committee Subjective Knee Form ». The 
American Journal of Sports Medicine 34 (10). 2006. (octobre): 1567̻1573.  
  
Ra, Ho Jong, Hyoung Soo Kim, Jung Yun Choi, Jeong Ku Ha, Ji Yeong Kim, et Jin Goo Kim  
« Comparison of the Ceiling Effect in the Lysholm Score and the IKDC Subjective Score for Assessing 
Functional Outcome after ACL Reconstruction ». The Knee 21 (5). 2014. (octobre): 906910.