Analysis of the Relationship Between Early Postoperative Anemia and the Evolution of Autonomy at 6 Months in Patients 75 Years of Age and Older Operated on Following a Fracture of the Upper End of the Femur
Conditions: Femoral Fracture
Sponsor: Centre Hospitalier Departemental Vendee

 
 
PAAF Project 
Analysis of the relationship between early post-operative anaemia 
and changes in independence at 6 months in patients aged 75 and 
over who have undergone surgery for a fracture of the upper end of 
the femur 
Non-interventional research 

 
 
PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
PAAF protocol 
Registration number: 2017-A03505-48 
Ref: CHD 117-17 
"Analysis of the relationship between early post-operative 
anaemia and changes in independence at 6 months in patients 
aged 75 and over who have undergone surgery for a fracture of 
the upper end of the femur" 
Coordinating Investigator: 
Dr Romain DECOURS 
Geriatrician 
Vendée Departmental Hospital Centre 
85925 La Roche sur Yon Cedex 9 
Romain.decours@chd-vendee.Fr 
Methodologist: 
Aurélie LE THUAUT 
Nantes University Hospital Research Centre 
53 chaussée de la Madeleine 
44000 Nantes 
Aurelie.le.thaut@chu-nantes.fr 
Sponsor: 
Vendée Departmental Hospital Clinical 
Research Unit Boulevard Stéphane 
MOREAU 
85 925 La Roche sur Yon Cedex 09 
Tel: 02 51 44 65 72 
Fax: 02 51 08 05 91 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
SIGNATURE PAGE 
SIGNATURE OF THE PROMOTER 
The sponsor undertakes to conduct this study in accordance with all legislative and 
regulatory provisions applicable to the research and in accordance with the protocol. 
Name and position of the signing 
representative: 
Date: 
Signature: 
Mr Francis SAINT-HUBERT 
Managing Director CHD Vendée 
SIGNATURE OF INVESTIGATORS 
I have read all the pages of the clinical trial protocol sponsored by CHD Vendée. I confirm that it 
contains all the information necessary to conduct the trial. I undertake to conduct the trial in 
accordance with the protocol and the terms and conditions set out therein. I undertake to conduct 
the trial in accordance with: 
❖ 
❖ 
the principles of the "Helsinki Declaration", 
the rules and recommendations of international (ICH) and French (rules of good clinical 
practice for biomedical research 
relating to medicinal products for human use) 
❖ European regulations and/or national legislation and regulations relating to clinical trials, 
I also undertake to ensure that investigators and other qualified members of my team have 
access to this protocol and to the documents relating to the conduct of the trial, so that they can 
work in accordance with the provisions contained in these documents. 
Name: 
Date: 
Date: 
Signature: 
Signature: 
Dr Romain DECOURS 
Coordinating 
Investigator 
Name and institution: 
Principal Investigator 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
LIST OF ABBREVIATIONS 
ADL 
Activities of Daily Living 
French National Agency for Medicines and Health Products Safety 
ANSM 
MA 
Marketing Authorisation 
ARC 
Clinical Research Associate 
ASA 
American Society of Anaesthesiologists 
Good Clinical Practice 
GCP 
CAM 
CHD 
CIRS - G 
CoDEx 
CSP 
Confusion Assessment Method 
Departmental Hospital Centre 
Cumulative Illness Rating Scale - Geriatrics 
Cognitive Disorder Examination 
Public Health Code 
CST 
CPP 
Transferrin Saturation Coefficient 
Committee for the Protection of Individuals 
CNIL 
French Data Protection Authority 
CRF 
CRP 
Case Report Form 
C-reactive protein 
Residential care homes 
Elderly 
for the Elderly 
Elderly Dependent 
for 
EHPAD 
EvIG 
SAE 
EIGI 
FESF 
IADL 
Serious Adverse Event 
Serious Adverse Effect 
Unexpected Serious Adverse Effect 
Fracture of the Upper End of the Femur 
Instrumental Activities of Daily Living 
International 
Conference 
(International Conference on Harmonisation) 
on 
Harmonisation 
ICH 
Nursing 
INSERM 
MiniGDS 
MR 
State-registered nurse 
National Institute of Health and Medical Research 
Mini Geriatric Depression Scale 
Reference Methodology 
NFS 
Complete Blood Count 
RCP 
SUSAR 
SLD 
Summary of Product Characteristics 
Suspected Unexpected Serious Adverse Reaction 
Long-term care 
SSR 
TEC 
Follow-up Care and Rehabilitation Service 
Clinical Research Technician 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
TABLE OF CONTENTS 
SIGNATURE PAGE................................................................................................................................................3 
LIST OF ABBREVIATIONS..................................................................................................................................4 
TABLE OF CONTENTS.........................................................................................................................................5 
INTRODUCTION....................................................................................................................................................6 
1 
2 
3 
. 
. 
. 
JUSTIFICATION FOR THE STUDY...........................................................................................................7 
1 
1 
.1. 
.2. 
POSITIONING OF THE RESEARCH ................................................................................................................7 
BENEFITS AND RISKS FOR INDIVIDUALS PARTICIPATING IN THE RESEARCH ..............................................9 
OBJECTIVES AND EVALUATION CRITERIA .....................................................................................13 
2 
2 
.1. 
.2. 
OBJECTIVE AND MAIN EVALUATION CRITERION......................................................................................13 
SECONDARY OBJECTIVES AND EVALUATION CRITERIA ...........................................................................14 
STUDY POPULATION................................................................................................................................15 
3 
3 
3 
.1. 
.2. 
.3. 
DESCRIPTION OF THE POPULATION ..........................................................................................................15 
INCLUSION CRITERIA ...............................................................................................................................15 
EXCLUSION CRITERIA ..............................................................................................................................15 
4 . 
STUDY DESIGN AND PROCEDURE .......................................................................................................16 
4 
4 
4 
4 
4 
4 
.1. 
STUDY SCHEDULE....................................................................................................................................16 
GENERAL RESEARCH METHODOLOGY .....................................................................................................20 
DETAILED DESCRIPTION OF THE EVALUATION AND DATA COLLECTED ...................................................20 
SPECIAL SITUATIONS ...............................................................................................................................23 
JUSTIFICATION FOR THE TELEPHONE CALL ..............................................................................................23 
IDENTIFICATION OF ALL SOURCE DATA NOT INCLUDED IN THE FILE 
.2. 
.3. 
.4. 
.5. 
.6. 
MEDICAL....................................................................................................................................................................................................23 
4 .7. 
RULES FOR DISCONTINUING A PERSON'S PARTICIPATION ........................................................................24 
5 
6 
. 
. 
DATA MANAGEMENT AND STATISTICS.............................................................................................25 
5 
5 
.1. 
.2. 
COLLECTION AND PROCESSING OF STUDY DATA .....................................................................................25 
STATISTICS ..............................................................................................................................................26 
MONITORING AND MANAGEMENT OF ADVERSE EVENTS.........................................................28 
6 
6 
6 
6 
.1. 
DEFINITIONS ............................................................................................................................................28 
LIST OF EXPECTED ADRS ........................................................................................................................29 
MANAGEMENT OF ADVERSE EVENTS.......................................................................................................30 
TERMS AND DURATION OF FOLLOW-UP OF PERSONS FOLLOWING THE OCCURRENCE OF ADVERSE EVENTS 
.2. 
.3. 
.4. 
31 
7 . 
ADMINISTRATIVE AND REGULATORY ASPECTS...........................................................................32 
7 
7 
7 
7 
7 
7 
7 
7 
7 
7 
7 
.1. 
RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS ...........................................................................32 
DATA CONFIDENTIALITY .........................................................................................................................32 
COMPUTERISED DATA AND SUBMISSION TO THE CNIL (FRENCH DATA PROTECTION AUTHORITY).........32 
MONITORING OF THE TRIAL.....................................................................................................................33 
INSPECTION/AUDIT..................................................................................................................................33 
ETHICAL CONSIDERATIONS......................................................................................................................33 
INFORMATION TO COMPETENT AUTHORITIES ..........................................................................................34 
AMENDMENTS TO THE PROTOCOL...........................................................................................................34 
FINANCING...............................................................................................................................................34 
RULES RELATING TO PUBLICATION .....................................................................................................34 
ARCHIVING OF SOURCE DATA..............................................................................................................35 
.2. 
.3. 
.4. 
.5. 
.6. 
.7. 
.8. 
.9. 
.10. 
.11. 
LIST OF APPENDICES .......................................................................................................................................36 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
INTRODUCTION 
Fractures of the upper femur (FUF) are a condition that becomes more common with age. It is a 
serious condition with multiple consequences, such as reduced life expectancy, quality of life and 
independence for patients. 
In this non-interventional study, we aim to evaluate changes in the independence of very elderly 
patients who have undergone surgery for a fracture of the upper end of the femur (FESF) in 
relation to early post-operative anaemia. 
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1. JUSTIFICATION FOR THE STUDY 
1.1. 
POSITIONING OF THE RESEARCH 
With the increase in life expectancy among the French population, there has been a rise 
in the number of patients with fractures of the upper femur (FESF), particularly among the elderly. 
In France, the number of hospital stays for UEF has been increasing by 0.3% per year since 
1 
4 
998, and the incidence remains predominantly female. The crude incidence rate of UEF was 
2.1/10,000 for people over 55 years of age in 2007. UEF mainly affects elderly and very elderly 
people. There has been a gradual increase in the average age of fracture patients. Again in 2007, 
patients over 80 years of age accounted for 60% of male patients operated on for FESF and 70% 
of female patients (1). This is a serious condition, with the risk of death increasing with age. It is 
2% in women under 80 during hospitalisation, rising to 8.3% in those over 95. This mortality rate 
is higher in men, reaching 15% in men over 94 during hospitalisation (1). Longer-term mortality 
rates vary according to studies, from 14.7% at one year (2) to 46% at one year in patients over 90 
years of age (3). However, there has been a gradual decrease in this mortality rate in France, 
probably due to improved surgical and perioperative care for patients (4). 
Anaemia is common in the geriatric population. In a survey of a hospitalised geriatric 
population, 24% of patients had anaemia, the aetiology of which was iron deficiency in 15% of 
cases (5). It is also common in surgery, particularly in the perioperative period. In a study of 546 
patients with fractures of the upper femur, 40.4% had anaemia on admission and 93.0% had 
anaemia postoperatively (6). 
Postoperative anaemia has multiple causes. It is probably aggravated by rehydration upon 
admission of patients with fractures (7). There is blood loss associated with the fracture and the 
formation of a haematoma prior to surgery (8), but also some postoperative occult bleeding: in 
546 patients with a fracture of the upper end of the femur, Foss et al. showed that post-operative 
occult bleeding ranged from 547 to 1473 mL, in addition to the blood loss observed during 
surgery. Finally, there is a degree of acute inflammatory anaemia secondary to surgery. This 
inflammatory component is caused by a decrease in progenitor proliferation, a reduced red blood 
cell half-life and iron retention by macrophages. This retention is mediated by ferritin, which is 
then increased, and by hepcidin, a recently discovered protein that regulates iron metabolism (9). 
Loss of independence, defined as a decrease in the ability to care for oneself, is also 
significant after a fracture of the upper end of the femur. Of 390 patients over the age of 65 who 
underwent surgery for an FESF and were analysed by Vochteloo's team, nearly half did not 
regain their previous independence after one year. Only 25% of patients who were mobile without 
assistance regained their previous independence within three months of surgery. Nineteen 
percent of patients became bedridden. The most significant risk factors were a low level of 
previous independence and the occurrence of postoperative confusion (10). 
The consequences of a loss of independence in elderly people are manifold (11). It leads to the 
intervention of outside help for activities of daily living, a change of living arrangements, a change 
in family relationships, and a risk of abuse by carers. The economic consequences are also 
significant: 
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health insurance expenditure for dependent elderly people was around €20.9 billion in 2011 (12). 
A patient's independence can be analysed in various ways. In the studies cited above, functional 
independence (walking) was prioritised because it was related to the condition being treated. 
However, in frail patients, overall independence is a key factor to measure because it affects 
quality of life and institutionalisation. Two scales can be used to measure this independence: 
Kartz's Activities of Daily Living and Lawton's Instrumental Activities of Daily Living. They take into 
account the patient's independence in performing daily activities alone or with assistance 
(washing, dressing, continence, eating, financial management, medication management, etc.). 
Anaemia appears to be associated with the independence of patients who have 
undergone FESF surgery, but few studies have analysed the relationship between post-operative 
anaemia and rehabilitation, especially in elderly subjects (13). However, it is known that anaemia 
in hospitalised medical patients is an independent factor in poor functional independence (14,15). 
There are numerous studies analysing the superiority or otherwise of a strict transfusion protocol 
(following standard transfusion guidelines) compared to a broader transfusion protocol 
(transfusing patients below the 10 g/dL threshold). This topic was recently addressed in a 
Cochrane literature review (16) (6 studies, 2,722 patients), which found no difference in mortality, 
functional recovery, or post-operative morbidity. 
This extensive research is based primarily on five studies attempting to establish a link between 
anaemia and functional autonomy, each of which used different assessments at different post- 
operative dates. 
- 
Lawrence (2003) retrospectively analysed a cohort of 5,793 patients over the age of 60 
from 1982 to 1993. It was shown that the average haemoglobin level during 
hospitalisation was associated with the walking distance covered upon discharge from 
hospital (p&lt;0.001 adjusted for age, Activities of Daily Living (ADL), neurological 
diseases, diabetes, Charlson and ASA comorbidities, beta-blocker treatment) [no 
reference to possible transfusions] (17). 
- 
Foss's work (2008) found a link between haemoglobin levels in the first three days post- 
operatively (487 patients, all ages combined) and patient mobility during those first three 
days (p&lt;0.05, before any transfusion). Independent risk factors for inability to walk were 
age over 75, dementia, reduced pre-fracture mobility, the presence of post-operative 
complications, and haemoglobin below 10 g/dL. Patients were treated according to a 
specialised perioperative rehabilitation protocol [surgery within 24 hours, spinal 
anaesthesia, epidural analgesia for 96 hours postoperatively, oral high-protein 
supplementation, daily 30-minute physiotherapy sessions from the first day] (18). 
Halm (2004) conducted a prospective observational study of 550 patients over the age of 
- 
- 
50. High pre- or post-operative haemoglobin levels were correlated with a reduction in 
length of hospital stay and readmission rates, but not with motor function scores (ability to 
walk and climb stairs, at day 60, assessed by telephone interview) [adjusted for age, sex, 
pre-fracture functional status, dementia, institutionalisation, transfusion] (19). 
Gruson (2002) showed that anaemia on admission in 395 patients over the age of 65 
(from 1991 to 1997) with a femoral neck fracture was correlated with a longer hospital 
stay and higher mortality at 6 and 12 months. A telephone call at 3, 6 and 12 months 
allowed for the assessment of an ADL and Instrumental Activities of Daily Living (IADL) 
score and functional autonomy, which were no different between anaemic and non- 
anaemic patients [patients who were previously autonomous, living at home and without 
cognitive impairment; based solely on anaemia on admission] (20). 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
- 
Maraldi (2006) analysed 56,752 patients over the age of 65 hospitalised in geriatrics 
(medicine sector). The recovery of independence at the end of hospitalisation was less 
significant in anaemic patients than in non-anaemic patients (p&lt;0.001). 
However, to our knowledge, no study has examined the association between the recovery of 
overall functional autonomy, as measured by ADL, and the post-operative haemoglobin level in 
the very elderly. The aim of these analyses is to improve our understanding of the loss of 
autonomy observed post-operatively following FESF, especially in the longer term, in order to 
manage it as effectively as possible. For example, at the Centre Hospitalier Départemental (CHD) 
in La Roche sur Yon, it would be interesting to optimise the transfusion protocols adopted within 
the hospital. There are also patient profiles where functional autonomy, and the resulting quality 
of life, is more important than mortality alone (in very elderly patients, for example, or those with 
multiple comorbidities). Furthermore, in our department, anaemia is a factor that limits patient 
mobility (sitting in a chair, physiotherapy), which probably has consequences for their early and 
future autonomy. The database could be used to set up interventional studies seeking to limit this 
loss of autonomy. 
In this study, we therefore propose to evaluate the impact of post-operative anaemia on the 
functional recovery of very elderly patients following surgery for a fracture of the upper end of the 
femur. 
1.2. 
BENEFITS 
AND RISKS 
FOR 
THE PEOPLE 
PARTICIPATING IN RESEARCH 
1.2.1. 
Benefits 
It is hoped that this study will improve understanding of the factors influencing the loss of 
independence commonly observed following a femoral neck fracture. 
The 
management 
of 
post-operative anaemia 
is 
not 
formalised, either in 
national 
recommendations or at institutional level. The aim of this study is to improve understanding of the 
repercussions of post-operative anaemia, but also to derive a standardised management 
protocol. This protocol must, in particular, determine the transfusion strategy for these fragile 
patients, in order to reserve blood transfusions for those who need them most, but above all to 
avoid less useful transfusions. 
1.2.2. 
Risks 
No risks related to the protocol are expected for the individuals participating in the research. The 
patient incurs the usual risks associated with the procedure and possible peri- and post-operative 
complications, including anaemia and its management, in the target population. 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
1.2.3. 
Benefit/risk balance 
The research manager classifies this research as non-interventional, since: 
All procedures are performed in the usual manner (blood sampling, interventions, etc.). 
✓ 
The research does not involve innovative or obsolete techniques or strategies. 
All patient care will be identical to standard practice. In particular, the discharge date will be 
decided by the physician in charge of the patient, independently of the study, but will be recorded 
in the patient's file and the research CRF. 
Consequently, the specific implementation procedures in the research represent negligible 
constraints for the person participating in the research. (Article R 1121-3 of the Public Health 
Code (CSP), Decree No. 2006-477 of 26 April 2006) 
The research manager shall therefore submit the study protocol to the South-East I 
Committee for the Protection of Persons (CPP) Sud-Est I for approval and confirmation of the 
research's eligibility, in accordance with Article L 1121-1 of the Public Health Code (CSP) as 
resulting from Laws No. 2004-806 of 9 August 2004 and No. 2006-450 of 18 April 2006 relating to 
public health policy. 
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BIBLIOGRAPHICAL REFERENCES 
1 . 
Oberlin Ph., Mouquet M.C. Femoral neck fractures in France between 1998 and 2007: 
what impact does ageing have? Studies Results. Apr 2010;(723). 
Kim S-M, Moon Y-W, Lim S-J, Yoon B-K, Min Y-K, Lee D-Y, et al. Prediction of survival, 
2. 
second fracture, and functional recovery following the first hip fracture surgery in elderly patients. 
Bone. June 2012;50(6):1343-50. 
3 . 
Jennings AG, de Boer P. Should we operate on nonagenarians with hip fractures? Injury. 
Apr 1999;30(3):169-72. 
Maravic M, Taupin P, Landais P, Roux C. Decrease in mortality among patients 
hospitalised for hip fractures in France. Rev Rhum. July 2011;78(4):368-72. 
Joosten E, Pelemans W, Hiele M, Noyen J, Verhaeghe R, Boogaerts MA. Prevalence and 
causes of anaemia in a geriatric hospitalised population. Gerontology. 1992;38(1-2):111 
4. 
5. 
- 7. 
6 
8 
7 
. 
Foss NB, Kehlet H. Hidden blood loss after surgery for hip fracture. J Bone Joint Surg Br. 
Jan 2006;88-B(8):1053-9. 
Odumala AO, Ayekoloye CI, Packer G. Predictors of excessive blood loss during 
. 
operative treatment of hip fractures. J R Coll Surg Edinb. June 2002;47(3):552-6. 
Smith GH, Tsang J, Molyneux SG, White TO. The hidden blood loss after hip fracture. 
Injury. 2011 Feb;42(2):133-5. 
Beaumont C, Karim Z. Current developments in iron metabolism. Rev Médecine Interne. 
Jan 2013;34(1):17–25. 
0. 
Vochteloo AJ, Moerman S, Tuinebreijer WE, Maier AB, de Vries MR, Bloem RM, et al. 
8. 
9. 
1 
More than half of hip fracture patients do not regain mobility in the first postoperative year. Geriatr 
Gerontol Int. 2013;13(2):334–341. 
1 
2 
1 
1. 
72 p. (Abstracts). 
2. 
High Council for the Future of Health Insurance. Health insurance and loss of autonomy: 
National College of Geriatric Teachers. Module 5: Ageing (2nd edition). Masson. 2010. 
HCAAM contribution to the debate on dependency among the elderly. June 2011. 
3. 
Potter LJ, Doleman B, Moppett IK. A systematic review of pre-operative anaemia and 
blood transfusion in patients with fractured hips. Anaesthesia. Apr 2015;70(4):483–500. 
4. 
Maraldi C, Ble A, Zuliani G, Guralnik JM, Mussi C, Fellin R, et al. Association between 
1 
1 
anaemia and physical disability in older patients: role of comorbidity. Aging Clin Exp Res. 2006 
Dec;18(6):485–92. 
15. 
Bailey RA, Reardon G, Wasserman MR, McKenzie RS, Hord RS. Association of 
anemia with worsened activities of daily living and health-related quality of life scores derived 
from the Minimum Data Set in long-term care residents. Health Qual Life Outcomes. 19 Oct 
2 
1 
012;10:129. 
6. 
Brunskill SJ, Millette SL, Shokoohi A, Pulford EC, Doree C, Murphy MF, et al. Red blood 
cell transfusion for people undergoing hip fracture surgery. Cochrane Database Syst Rev. 
2 
1 
015;4:CD009699. 
7. 
Lawrence VA, Silverstein JH, Cornell JE, Pederson T, Noveck H, Carson JL. Higher Hb 
level is associated with better early functional recovery after hip fracture repair. Transfusion 
(Paris). 2003;43(12):1717–1722. 
1 8. 
surgery. Age Ageing. 3 Jan 2008;37(2):173–8. 
9. 
Halm EA, Wang JJ, Boockvar K, Penrod J, Silberzweig SB, Magaziner J, et al. The 
Foss NB, Kristensen MT, Kehlet H. Anaemia impedes functional mobility after hip fracture 
1 
effect of perioperative anaemia on clinical and functional outcomes in patients with hip fracture. J 
Orthop Trauma. July 2004;18(6):369-74. 
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2 0. 
admission haemoglobin level and outcome after hip fracture. J Orthop Trauma. Jan 
002;16(1):39-44. 
1. 
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the 
Gruson KI, Aharonoff GB, Egol KA, Zuckerman JD, Koval KJ. The relationship between 
2 
2 
aged. The index of ADL: a standardised measure of biological and psychosocial function. JAMA J 
Am Med Assoc. 21 Sept 1963;185:914-9. 
2 2. 
activities of daily living. The Gerontologist. 1969;9(3):179–86. 
3. 
Foss NB, Kristensen MT, Kehlet H. Prediction of postoperative morbidity, mortality 
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental 
2 
and rehabilitation in hip fracture patients: the cumulated ambulation score. Clin Rehabil. 8 Jan 
2 006;20(8):701–8. 
2 4. 
Hillman TE, Nunes QM, Hornby ST, Stanga Z, Neal KR, Rowlands BJ, et al. A 
practical posture for hand grip dynamometry in the clinical setting. Clin Nutr Edinb Scotl. Apr 
005;24(2):224–8. 
5. 
Hoffer MM, Feiwell E, Perry R, Perry J, Bonnett C. Functional ambulation in patients with 
myelomeningocele. J Bone Joint Surg Am. Jan 1973;55(1):137–48. 
6. 
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying 
2 
2 
2 
confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern 
Med. 15 Dec 1990;113(12):941-8. 
2 7. 
validation of a French version. Perspectives infirmières. Oct 2005;12–22. 
8. 
Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. May 
968;16(5):622–6. 
9. 
Salvi F, Miller MD, Grilli A, Giorgi R, Towers AL, Morichi V, et al. A manual of 
Laplante J, Cole M, McCusker J, Singh S, Ouimet MA. Confusion Assessment Method 
2 
1 
2 
Guidelines for scoring the modified cumulative illness rating scale and its validation in acute hospitalised 
elderly patients. J Am Geriatr Soc. Oct 2008;56(10):1926–31. 
3 0. 
Owens WD, Felts JA, Spitznagel EL. ASA physical status classifications: a study of 
consistency of ratings. Anesthesiology. Oct 1978;49(4):239–43. 
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2. OBJECTIVES AND EVALUATION CRITERIA 
2.1. 
OBJECTIVE AND PRIMARY ENDPOINT 
2.1.1. 
Primary objective 
The primary objective is to analyse the relationship between the severity of early postoperative 
anaemia and functional independence at 6 months postoperatively in elderly patients who have 
undergone surgery for a fracture of the upper femur. 
2.1.2. 
Primary evaluation criterion 
⮚ 
⮚ 
Haemoglobin level on day 5 post-operatively (considered the post-operative haemoglobin 
reference level in this study) 
▪ 
In the case of patients who received a transfusion postoperatively, the 
reference haemoglobin level will be the haemoglobin level at the end of 
hospitalisation 
Change in the Activities of Daily Living (ADL) score pre-fracture and 6 months post- 
operatively. 
A loss of independence will be defined as a decrease of one point or more in the ADL. 
The reference value for haemoglobin levels was arbitrarily set at 5 days post-operatively. This is 
because haemoglobin levels recorded in A&E or on admission to the ward prior to surgery, or 
immediately post-operatively, may be influenced by factors other than isolated anaemia. 
Dehydration, present in the emergency department or on admission to the ward before the 
operation, corrected preoperatively, and postoperative haemodilution due to fluid replacement, 
cause the haemoglobin level to vary without there being any real deglobulation. We therefore 
postulate that the haemoglobin level on the 5th postoperative day can serve as a reference. 
Confounding factors collected 
All confounding factors related to loss of autonomy will be collected: 
- 
Transfusion and number of red blood cell concentrates received 
The indication for transfusion is at the discretion of the prescriber. However, it is generally 
accepted to transfuse patients with haemoglobin levels below 8 g/dL, or below 10 g/dL in cases of 
ischaemic heart disease or poor clinical tolerance. 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Age 
Gender 
Height, weight, Body Mass Index (BMI) calculation 
Screening for past or present higher brain function disorders 
Screening for major sensory disorders 
Screening for depressive symptoms: Mini Geriatric Depression Scale (MiniGDS) 
Comorbidities assessed using the Cumulative Illness Rating Scale - Geriatrics (CIRS-G) 
ASA score 
Number 
of 
medications 
(per 
class) 
taken by 
the patient 
(anticoagulants, 
antiplatelet agents, NSAIDs, anti-osteoporotic drugs, analgesics) 
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- 
- 
- 
- 
- 
Lifestyle and living environment 
Severe fractures before and after inclusion 
Other falls during the year 
Protein-energy malnutrition 
Iron deficiency (ferritin < 30 µg/L or CRP > 20 mg/L associated with a transferrin 
saturation coefficient < 15%) 
- 
Recurrence of falls at 1, 3 and 6 months post-op 
2.2. 
SECONDARY OBJECTIVES AND EVALUATION CRITERIA 
2.2.1. 
Secondary objectives 
The secondary objectives are to analyse: 
- the influence of post-operative anaemia: 
- 
on independence in elderly patients who have undergone surgery for a fracture of the 
upper end of the femur upon discharge from hospital, at 1 month and 3 months post- 
operatively 
- 
on mortality 6 months after surgery 
- the progression of post-operative anaemia 
2.2.2. 
Secondary evaluation criteria 
⮚ Lowest postoperative haemoglobin level recorded on admission to the emergency 
department, on admission to the ward, on D0 (day of surgery), D1, D3, D5, D10 and D15 
(postoperative days) 
). 
The severity of anaemia will be defined as follows: 
o 
o 
o 
o 
greater than 12 g/dL, 
less than or equal to 12 g/L 
less than or equal to 8 g/L 
less than 8 g/dL (and therefore requiring a transfusion) 
⮚ 
⮚ 
Assessment of Activities of Daily Living (ADL): pre-fracture, on day 5 post-operative (or on 
discharge from hospital if discharged before day 5) at 1 month, 3 months and 6 months 
post-operative. 
Assessment of instrumental Activities of Daily Living (IADL): pre-fracture, 
at 1 
month, 3 months and 6 months post-operative. 
Loss of independence will be defined as a decrease of one point or more in the ADL 
and/or IADL. 
⮚ Vital status at 6 months post-operatively 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
3. STUDY POPULATION 
3.1. 
DESCRIPTION OF THE POPULATION 
This study is intended for patients over the age of 75 who have undergone surgery for a fracture 
of the upper end of the femur. 
3.2. 
INCLUSION CRITERIA 
- 
- 
- 
- 
- 
Patients aged 75 years and older, regardless of gender. 
Patients who have undergone surgery for a fracture of the upper end of the femur. 
Patients, family members or trusted relatives who do not object to participation in the study 
Patients affiliated with a social security scheme 
Patients who can be monitored within the framework of the protocol 
3.3. 
EXCLUSION CRITERIA 
- 
- 
- 
- 
- 
- 
- 
Refusal to participate in the study (patient, family or trusted relative) 
Patient with weight-bearing on the operated limb not authorised by the surgeon 
Patient with an associated fracture (multiple trauma, concomitant trauma to the upper limb, etc.) 
Patient with a pathological fracture 
Patient included in a category 1 interventional study (involving a drug or medical device) 
Patient deprived of liberty 
Patients not affiliated with a social security scheme 
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4. STUDY DESIGN AND PROCEDURE 
4.1. 
STUDY SCHEDULE 
The inclusion period will be 42 months. Follow-up is 6 months post-operative. 
Patients may be included up to 48 hours after their arrival in the orthopaedic/orthopaedic surgery 
department. 
a. D0 - Arrival in the orthopaedic/orthopaedic surgery department (after surgery) 
Provision of the information leaflet and collection of non-objection after a reflection period. 
Completion of the ASA score (investigator) 
Biological tests (complete blood count (CBC), CRP, ferritin, transferrin saturation coefficient, 
albumin, vitamins B12, folate and vitamin D) (investigator – performed on arrival at A&E or on 
admission to the department before surgery) 
Record of severe fractures prior to inclusion: upper end of the femur or humerus, proximal tibia, 
distal femur, 3 simultaneous ribs, wrist, pelvis and spine (Grio 2011 recommendations) 
(investigator) 
Screening for previous or current upper function disorders (investigator) 
Screening for major sensory disorders (investigator) 
Completion of ADL and IADL questionnaires: information relating to the week preceding the 
intervention (investigator: interview with patient, family or staff of residential care homes for 
elderly dependents (EHPAD)) 
Completion of the CIRS-G score (investigator) 
Completion of the CAS questionnaire 
Recording of lifestyle and living environment (investigator) 
Number of medications (by class) taken by the patient on admission (anticoagulants, antiplatelet 
agents, NSAIDs, anti-osteoporotics, analgesics) (investigator) Completion of the MiniGDS score 
(investigator) 
Collection of data on the procedure: time to surgery, type of fracture, surgical procedure, type of 
anaesthesia, weight-bearing authorisation, transfusion, number of red blood cell units received 
Haemoglobin measurement (if different from that taken in the emergency department or on 
admission to the ward before the procedure) 
b. During the hospital stay:  (trained orthopaedic nurses) 
CAS score performed on days 1 to 3 post-operative, as well as on day 5 (or on discharge if this 
occurs before day 5) 
Daily screening for confusion (CAM) until D10 if the patient is still hospitalised Completion of ADL 
questionnaires (patient, family or nursing home resident interview) on D5 post-operative (or on 
discharge if this occurs before D5) 
Measurement of grip strength – Hand Grip on day 5 (or upon discharge if this occurs before day 
5) 
Record of falls occurring during hospitalisation 
Record transfusions and number of red blood cell concentrates Measure 
haemoglobin levels on days 1, 3, 5, 10 and 15 after surgery 
Recording of Venofer® administration on day 5 (or on discharge if this occurs before day 5) 
Recording of post-operative complications: post-operative infection requiring antibiotic therapy 
(surgical site, pulmonary, urinary, skin, other), acute urinary retention requiring catheterisation, 
dislocation/loosening of prosthesis, iron deficiency (ferritin < 30 µg/L or CRP > 20 µg/L) 
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PAAF Protocol – Dr. DECOURS – Version 6.0 dated 19/03/2021 
requiring urinary catheterisation, dislocation/loosening of prosthesis, iron deficiency (ferritin < 30 
µg/L or CRP > 20 mg/L associated with a transferrin saturation coefficient < 15%) and/or vitamin 
deficiency (B12 < laboratory threshold, B9 (folate) < 3.5 ng/mL), cardiovascular/neurological 
complications, post-operative bleeding (including local and digestive), reoperation, haematomas. 
Prescription for haemoglobin monitoring on days 5, 10 and 15 post-operatively if the patient has 
been discharged from hospital 
Time allowed for completion: +/- 2 days 
c. At the end of hospitalisation: (investigator) 
Number of medications (by class) (anticoagulants, antiplatelet agents, NSAIDs, anti- 
osteoporotics, analgesics) 
Screening for current higher brain function disorders Record of 
length of hospital stay 
Record of discharge status 
Record of vital status 
d. Follow-up telephone call 1 month and 3 months  post-operative (supplemented if 
necessary by questioning the patient, family or nursing home staff) 
Record of living arrangements and location 
Completion 
questionnaires 
questionnaire 
of 
ADL 
Completion 
and 
of 
IADL 
CAS 
Investigation of late post-operative complications: infection requiring antibiotic treatment (surgical 
site, pulmonary, urinary, skin, other), acute urinary retention requiring urinary catheterisation, 
dislocation/loosening of prosthesis, cardiovascular/neurological complications, reoperation. 
Record of recurrent falls or fractures New 
hospitalisation and reason for hospitalisation Record of 
vital status 
e. Telephone follow-up 6 months post-operative  (supplemented if necessary by 
questioning the patient, family or nursing home staff) 
Record of lifestyle and living arrangements 
Completion of ADL and IADL questionnaires 
Completion of CAS questionnaire 
Search for late post-operative complications: infection requiring antibiotic treatment (surgical site, 
pulmonary, urinary, skin, other), acute urinary retention requiring urinary catheterisation, 
dislocation/loosening of prosthesis, cardiovascular/neurological complications, reoperation. 
Record of recurrent falls or fractures New 
hospitalisation and reason for hospitalisation 
Number of medications (by class) taken by the patient (anti-osteoporotic, analgesic) Vital status 
record 
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STUDY TIMELINE 
D 
M1, M3 and M6 
post-op 
(+/- 15 days) 
Telephone 
follow-up 
Arrival in the 
orthopaedic 
surgery 
department 
(day of surgery) 
From D1 to 
D4 
post-op. 
Day 5 
post- 
op** 
End of 
hospitalisation 
Actions 
Information for patient/family/trusted relative Collection of 
non-objection form 
ADL 
X  * 
X 
X 
1 
1 
X 
X 
X 
IADL 
CAS 
X 
X  1 
X 
X 
X 
(from D1 to D3) 
HandGrip Test 
ASA score/CIRS-G score/MiniGDS score 
Confusion screening (CAM) 
X 
X (daily – up to day 10 if patient is still 
hospitalised) 
Screening for previous or current higher brain function disorders 
Check for major sensory disorders 
Haemoglobin 
X 
X 
X 
X 
X (D1, D3, D5, D10, D15) 
NFS, CRP, albumin, ferritin, transferrin saturation coefficient, vitamins 
B12, folates and vitamin D 
Information about the procedure2 
X 
X 
Post-operative complications 
X 
X 4 
(daily)3 
Fractures/falls 
X (fractures) 
X (daily) 
X 
Length of hospital stay/Discharge status 
Re-hospitalisation and reason 
Concomitant treatments 
Vital status 
X 
X 
X 
X(M6)6 
X 
X 5 
X (End of hospitalisation)5 
X 
X 
* 
* 
1 
2 
3 
Can be performed up to 48 hours after arrival at the department 
* Five days after surgery or upon discharge from hospital if this occurs before five days 
: Information relating to the week preceding the operation 
: Time of surgery, type of fracture, surgical procedure, type of anaesthesia, weight-bearing authorisation, transfusion, number of red blood cell units received 
: Post-operative infection requiring antibiotic treatment (surgical site/pulmonary/urinary/skin/other), acute urinary retention requiring urinary catheterisation, 
dislocation/loosening of prosthesis, iron and/or vitamin deficiencies, transfusion, number of packed red blood cell units received, cardiovascular/neurological 
complications, post-operative bleeding (including local and digestive), reoperation, haematomas, 
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4 Infection requiring antibiotic therapy (surgical site/pulmonary/urinary/cutaneous/other), acute urinary retention requiring urinary catheterisation, dislocation/loosening 
of prosthesis, cardiovascular/neurological complications, repeat surgery, 
4 5 : anticoagulants, antiplatelet agents, NSAIDs, anti-osteoporotic agents, analgesics 
: anti-osteoporosis drugs, analgesics 
6 
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4.2. 
GENERAL RESEARCH METHODOLOGY 
The research has the following characteristics: 
❖ 
❖ 
❖ 
Multicentre study 
Prospective study 
Uncontrolled study 
❖ Non-randomised study 
4.3. 
DESCRIPTION 
DETAILED 
OF 
THE EVALUATION AND THE 
DATA COLLECTED 
a. On patient autonomy: 
- 
Activities of Daily Living (ADL) (21): Measured at inclusion (information relating to the 
week preceding the procedure) (questioning of patient, family, nursing home staff), on 
day 5 post-op (or on discharge from hospital if discharged before day 5) (in hospital), 1 
month, 3 months and 6 months post-op (telephone call). 
Validated scale for assessing independence in simple activities of daily living: hygiene, dressing, 
mobility, going to the toilet, continence, eating. Each item is coded as follows: 
1: done independently 
0.5: done partially or with assistance 
0: not done 
Scale ranging from 0 to 6, with a high score indicating a more independent patient. 
- Lawton's 4-item Instrumental Activities of Daily Living (IADL) (22): Measured at inclusion 
(information relating to the week preceding the intervention) (questioning of patient, 
family, nursing home staff), at 1 month, 3 months and 6 months post-operatively 
(telephone call). 
Validated scale for assessing patient autonomy in so-called "instrumental" activities of daily living: 
managing finances, preparing medication, using the telephone, using transport. Each item is coded 
as follows: 
1 
0 
0 
: done alone 
.5: does partially or with assistance 
: does not do 
The score ranges from 0 to 8. A high score indicates that the patient is independent. This score can 
only be interpreted for subjects living at home. 
- Cumulative Ambulation Score (23): Measured at inclusion (information relating to the week 
preceding the procedure), from D1 to D3 post-operative, on D5 post-operative (or on discharge if 
before D5) (in-hospital), and at 1 month, 3 months and 6 months (telephone call) 
Validated score predictive of mortality, morbidity and rehabilitation. Three areas (transfer from lying 
to sitting, transfer from sitting to standing, walking with appropriate aids) are assessed from 0 (unable 
despite the help of two people) to 2 (able to do independently). The scores are cumulative over the 
first 3 days post-operatively and give a score of 0 to 18. A cumulative score greater than 10 
corresponds to a 99% probability that the patient will be alive at one month, 93% that they will have 
returned home, and 94% that they will not have had any major post-operative complications. 
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b. On the patient's physical performance: 
- 
Measurement of grip strength (Hand Grip) on day 5 post-operatively (or on discharge 
from hospital if this occurs before day 5) (in-hospital). 
This is measured using a dynamometer. Patients, in a lying or sitting position, are encouraged to 
squeeze as hard as they can. The best value from three attempts with the dominant hand is used for 
analysis. The assessment of grip strength using a suitable dynamometer has shown good 
reproducibility and validity for elderly hospitalised subjects (24). 
c. Regarding the surgical procedure: 
- 
Time to surgery (time between admission to the emergency department or admission to the 
ward prior to surgery and the surgical procedure) 
- 
* 
* 
- 
* 
* 
- 
Types of fractures: 
Intracapsular fracture (or true cervical fracture): Garden classification I to IV 
Extracapsular (or per-trochanteric) fracture: true trochanteric or trochanteric-diaphyseal 
Surgical procedures: 
total or intermediate hip replacement arthroplasty, with or without cement 
Osteosynthesis 
- 
- 
- 
- 
Spinal regional anaesthesia or general anaesthesia 
Need for intraoperative or immediate postoperative transfusion (recovery room) 
Authorisation for weight-bearing (surgical instructions) 
Record of transfusions and the number of red blood cell concentrates administered 
(intraoperative and perioperative – in the recovery room). 
d. Regarding hospitalisation and complications: 
- 
- 
Length of hospitalisation 
Occurrence of acute postoperative confusion - daily and up to day 10 if the patient is still 
hospitalised (screened during hospitalisation using the Confusion Assessment Method CAM 
scale)(26,27). 
This is a diagnostic aid, which can be carried out by a nurse, looking for the presence of sudden and 
fluctuating symptoms, inattention, disorganised thinking and/or disturbances of consciousness. The 
presence of the first two criteria and the third or fourth criterion leads to a diagnosis of acute 
confusional syndrome. 
During hospitalisation: 
- 
Occurrence of a post-operative infection (surgical site, pulmonary, urinary, skin, other) 
requiring antibiotic therapy. 
- 
- 
- 
Occurrence of acute urinary retention requiring urinary catheterisation 
Occurrence of dislocation/loosening of prosthesis 
Screening for iron deficiency (ferritin < 30 µg/L, CRP > 20 mg/L associated with a transferrin 
saturation coefficient < 15%) or vitamin deficiency (vitamin B12 < laboratory threshold and B9 
(folate) < 3.5 ng/mL) 
- 
Record of transfusions and number of red blood cell concentrates administered. 
- 
Occurrence of cardiovascular complications: deep vein thrombosis, pulmonary embolism, 
myocardial ischaemia (increased troponin). 
- 
- 
- 
- 
- 
- 
Occurrence of a neurological complication: stroke, cerebrovascular accident, etc. 
Post-operative bleeding (including localised bleeding and gastrointestinal bleeding) 
Need for repeat surgery 
Occurrence of haematomas 
Record of falls 
Vital status 
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Post-operative M1, M3 and M6: 
- 
Occurrence of infection (surgical site, pulmonary, urinary, skin, other), requiring antibiotic 
therapy. 
- 
- 
- 
Occurrence of acute urinary retention requiring urinary catheterisation 
Occurrence of dislocation/loosening of prosthesis 
Occurrence of a cardiovascular complication: deep vein thrombosis, pulmonary embolism, 
myocardial ischaemia (increased troponin) 
- 
- 
- 
- 
- 
- 
Occurrence of a neurological complication: stroke, etc. 
Need for repeat surgery 
Record of recurrent falls or fractures 
Record of new hospitalisations and reasons 
Vital status 
e. On geriatric assessment 
- 
CIRS-G(28) scale (in-hospital - inclusion): 
This is a comorbidity scale frequently used in studies because it provides a description of the health 
status of a population, describing chronic conditions and diseases that have an impact on autonomy, 
with good reliability and reproducibility 
(29). For 14 major systems or groups of systems (cardiac, vascular, pulmonary pathologies, etc.), a 
score out of 4 is given: 1 being a mild pathology (chronic sinusitis or smoking less than 20 pack- 
years, for example), 4 is a severe condition causing disability or requiring immediate treatment (acute 
urinary retention or stroke with hemiparesis). 
- 
ASA score (30) (in-hospital - inclusion) 
Scale used in anaesthesiology Classifying patients into 6 categories: 1: healthy 
patient, 
2 
3 
4 
5 
6 
- 
: with moderate impairment of a major function, 
: patient with severe impairment of a major function that does not result in disability, 
: patient with severe impairment of a major function, which is disabling and life-threatening, 
: moribund patient, 
: patient declared brain dead whose organs are being harvested for transplantation. 
Screening for depressive symptoms: MiniGDS score (intra-hospital – inclusion). 
Screening for previous and current higher function disorders by interviewing family and 
- 
friends or consulting the patient's file (in-hospital – inclusion and during hospitalisation). 
- 
Screening for major sensory disorders (in-hospital – inclusion). 
- 
Number of medications (by class) taken by the patient at inclusion and at the end of 
hospitalisation, including anticoagulant therapy, antiplatelet therapy, NSAIDs, anti-osteoporotic 
therapy, analgesics, and at 6 months post-operatively, including anti-osteoporotic and analgesic 
therapy. 
- 
Patient's living arrangements (in hospital – inclusion and at 1, 3 and 6 months): alone, with 
family or partner, widowed, in a care home. Home help for shopping, cleaning and personal care. 
Patient discharge arrangements (in-hospital – end of hospitalisation): return home, return 
to care facility, transfer to follow-up care unit. 
Previous osteoporotic fractures (in-hospital – inclusion): low-energy fractures of the hip, 
wrist, vertebral body or humerus. 
Albumin level (assessment upon admission, coupled with CRP): a level below 35g/L upon 
admission indicates protein-energy malnutrition. 
Recurrence of falls or fractures at 1 month, 3 months and 6 months post-operatively 
(telephone call). 
- 
- 
- 
- 
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4.4. 
SPECIAL SITUATIONS 
Dementia patients: the interview with dementia patients will be completed by their family or nursing 
home staff. Information about participation in the study will be provided to the family/trusted relative. 
If surgery is postponed  (due to the patient's general condition or the presence of antiplatelet or 
anticoagulant treatment, for example), D0 remains the date of the procedure and corresponds to the 
patient's return to the orthopaedic/orthopaedic surgery department (after the procedure). 
If the patient is discharged early, a standardised prescription will allow haemoglobin to be monitored 
on D5, D10 and D15 (timeframe: +/- 2 days). 
A patient may receive a transfusion, 
- 
- 
pre- or peri-operative transfusion in the recovery room 
post-operative transfusion 
▪ 
In hospital: during the orthopaedic stay 
▪ 
Post-hospital: new hospitalisation required for transfusion 
4.5. 
REASON FOR THE TELEPHONE CALL 
This study is aimed at elderly and often frail patients. The participating centres are referral centres 
that treat patients from all regions. For the most optimal and objective recovery possible, the 1- 
month, 3-month and 6-month assessments should have taken place during a geriatric consultation. 
Due to the likely frailty of the patients, the absence of systematic post-hospitalisation surgical 
consultations, and the sometimes significant distance from the patients' place of residence, we felt it 
was reasonable to limit this follow-up to a telephone follow-up, either with the patient, their family or 
the nursing staff at the nursing home. Thus, the telephone assessments are based on simple criteria 
that can be assessed over the phone. 
It should be noted that follow-up, including autonomy, was also carried out by telephone during the 
study by Halm et al. (19). 
4.6. 
IDENTIFICATION OF ALL SOURCE DATA NOT INCLUDED IN THE 
MEDICAL RECORD 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Lifestyle and living environment 
Previous fractures 
Screening for previous or current higher brain function disorders 
Screening for major sensory disorders 
Screening for depressive symptoms (mini GDS) 
Handgrip strength measurement 
ASA/CIRS-G/CAS/ADL/IADL score 
Screening for confusion (CAM) 
Discharge mode 
Late post-operative complications 
Recurrence of falls or fractures 
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4.7. 
RULES FOR DISCONTINUING A PERSON'S PARTICIPATION 
4.7.1. 
Criteria for premature termination of a person's 
participation in the research 
Any patient included in the protocol who no longer wishes to participate will be withdrawn from the 
study as soon as they express their request. 
4.7.2. 
Procedures 
for 
of 
of 
participation 
participation of a person in the research 
For the terms and conditions governing the use of data from individuals who have withdrawn 
prematurely from the study, please refer to the statistics section. 
4.7.3. 
Criteria for discontinuing part or all of the research 
(excluding biostatistical considerations) 
Part or all of the study may be terminated permanently or temporarily by decision of the French 
National Agency for Medicines and Health Products Safety (ANSM), the CPP, or the study sponsor. 
In all cases: 
- Written confirmation will be sent to the study's coordinating investigator (specifying the reasons for 
early termination). 
All patients in the study will be informed and will be required to attend their early exit visit. 
- 
To complete this section, refer to the "statistics" section, which presents the statistical criteria for 
stopping the research. 
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5. DATA MANAGEMENT AND STATISTICS 
5.1. 
COLLECTION AND PROCESSING OF STUDY DATA 
5.1.1. 
Data collection 
An electronic case report form (eCRF) will be created for each patient. All information required by the 
protocol must be provided in the eCRF. It must include the data necessary to confirm compliance 
with the protocol and all data necessary for statistical analysis; it must allow for the detection of major 
deviations from the protocol. 
The person(s) responsible for completing the eCRF (investigator, ARC, etc.) must 
be defined and identified in the table of delegated responsibilities for each centre (kept in the 
investigator's binder). 
5.1.2. 
Data coding 
By signing this protocol, the principal investigator and all co-investigators undertake to keep the 
identities of the patients who participated in the study confidential. 
Each patient included in the study will be assigned an incremental code consisting of the following 
three items: treatment centre number, serial number, initials (first letter of surname and first letter of 
first name). 
This code will be the only information that will appear on the electronic case report form (eCRF) and 
will enable the eCRF to be linked to the patient at a later date. 
The investigator is also required to code patient data on all documents in their possession (imaging 
reports, biology reports, etc.) that are attached to the eCRF. 
5.1.3. 
Data processing 
Clinical data collection will be based on the establishment of a database and the creation of data 
entry forms modelled on the observation log, in accordance with the protocol and regulations 
currently in force. 
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5.2. 
STATISTICS 
Statistical analyses will be performed by Lucie PLANCHE, Statistical Engineer at the Vendée 
Departmental Hospital Centre. 
Statistical analyses will be performed using R software version 3.5.3. 
5.2.1. 
Description of 
methods 
planned 
planned, 
including the schedule for planned interim analyses 
All variables collected will be described by minimum, maximum, quartiles, mean and standard 
deviation for quantitative variables and by number and percentage of each modality for qualitative 
variables. 
Analysis of the primary endpoint: 
The relationship between loss of independence at 6 months and post-operative anaemia will be 
analysed using a logistic model. If a link is found, a multivariate analysis will be performed to confirm 
the independence of the anaemia/independence relationship. To do this, all potential confounding 
factors will be tested in a univariate analysis. Factors associated with a p value <0.20 will be retained 
in the multivariate model. 
Analysis of secondary criteria: 
- The analysis of the relationship between loss of autonomy on day 5 (or on discharge from hospital 
if discharged before day 5), at 1 and 3 months, and post-operative anaemia will be performed using 
the same method as for the primary endpoint. 
- 
The 6-month mortality rate will be estimated with its 95% confidence interval using the 
Kaplan-Meier method. 
The association between anaemia and mortality at 6 months will be studied using a Cox proportional 
hazards model in order to take confounding factors into account. 
- The progression of post-operative anaemia (D0 to D15) will be described graphically. 
5.2.2. 
Statistical justification for the number of inclusions 
According to data from the Medical Information Department (DIM) of the CHD in La Roche Sur Yon, 
over an inclusion period of 18 months, 320 patients aged over 75 underwent surgery on the upper 
end of the femur (210 patients per year, on average over the last 4 years of activity). 
Assuming a mortality rate of 10% and a loss to follow-up rate of 10%, 255 patients could be 
analysed. 
According to Gruson (20), 67.8% of patients regained their previous level of independence within 12 
months, while 6.3% died within 6 months. 
According to Halm (19), 65% of patients had post-operative anaemia of less than 10g/dL. 
As the presence of at least 10 events (loss of independence) per criterion selected in the multivariate 
analysis is recommended, the inclusion of 255 patients appears to be consistent. 
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5.2.3. 
Expected degree of statistical significance 
The significance threshold is set at 5%. 
5 .2.4. 
unused or invalid data 
Method 
of 
into account 
of 
missing, 
No imputation will be performed on missing data. These will be described in terms of numbers and 
percentages. 
5.2.5. 
Selection of individuals to be included in the analyses 
All patients for whom preoperative and 6-month loss of autonomy is recorded will be included in the 
analysis. 
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6. MONITORING AND MANAGEMENT OF 
ADVERSE EVENTS 
6.1. 
DEFINITIONS 
Vigilance 
This refers to the monitoring of medicines, medical devices and 
other health-related products 
It 
also consists 
of 
prevention of the risk of adverse effects resulting from their use, 
whether this risk is potential or proven, 
Adverse events 
(AE) 
Any harmful event occurring in a person participating in research 
involving human subjects, whether or not the event is related to the 
research or the product being researched. 
Adverse effects (AE) 
An adverse event occurring in a person participating in research 
involving human subjects, when 
this event is related to the research or the product being 
researched. 
Serious Adverse Effects/Events Any adverse effect/event that: 
(SAE)/(SAE) 
* results in death, 
* is life-threatening, 
* causes temporary or permanent incapacitation or 
disability, 
* 
* 
* 
requires or prolongs hospitalisation of the patient, 
causes a congenital or neonatal abnormality, 
is medically significant (the list of medically significant 
effects/events is defined by the EMA). 
Unexpected adverse effects 
(UEAEs) 
Any adverse effect whose nature, severity or progression is 
inconsistent with the information relating to the products, 
procedures and methods used during the research. 
New information 
Any new data that could lead to a reassessment of the benefits 
and risks of the research or the product being researched, to 
changes in the use of this product, in the conduct of the research, 
or in the documents relating to the research, or to the suspension, 
interruption or modification of the research protocol or similar 
research. For trials involving the first administration or use of a 
health product in 
people who do not have any medical conditions: any serious 
adverse effect. 
Abuse 
Intentional, persistent or sporadic excessive use of a drug that is 
accompanied by harmful physical or psychological reactions. 
Overdose 
Administration of a quantity of a drug, given in a single dose or 
cumulatively, that is above 
above the maximum recommended dose according to the rules of 
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compliance or use of the product. Clinical judgement should always 
be applied. 
(actual overdose: due to an excessive gross quantity 
/ relative overdose: due to predisposing factors in the patient such 
as renal failure, hypoalbuminaemia, etc.) 
Misuse or off-label use 
A situation where the product is intentionally used in a manner that 
does not comply with the product's specifications for use (e.g. 
route of administration/dosage or indication different from 
those listed in the reference document) 
Medication error 
(ME) 
Refers to any proven (or potential) omission or unintentional action 
that occurred during the care process, in the chain (from 
manufacture to administration) involving a product that may cause 
a risk or adverse event for the patient. The risk of error or potential 
error refers to situations where the error did not occur, was 
intercepted but could have 
have occurred 
6.2. 
LIST OF EXPECTED ADVERSE EVENTS 
No complications are expected from the protocol procedure, which consists of analysing the 
relationship between early post-operative anaemia and functional autonomy at 6 months post- 
operatively. 
A malfunction in the information collection or data analysis system could have a detrimental impact 
on the results but would not be harmful to the patients included. 
The expected adverse events related to the patient's condition, the procedure and its possible 
complications and their management, co-morbidities and ancillary treatments are no different from 
those observed in the population routinely treated for the same condition. 
Post-operative AEs may be directly related to surgery, anaesthesia, associated treatments 
including analgesics, but may also be related to the patient's previous condition and 
comorbidities: 
- 
- 
- 
- 
- 
haematomas and bleeding at the surgical site 
infection of the surgical site 
local or regional pain 
limited movement 
sciatic nerve paralysis 
Related to anaesthesia: in addition to the risk of immediate hypersensitivity, delayed awakening, 
drowsiness, confusion, etc., the adverse effects of the various drugs used are listed in the respective 
drug summaries of product characteristics. 
Related to pain relief treatment: confusion, drowsiness, dizziness, nausea, etc. The adverse effects 
of the various drugs used are listed in the respective summaries of product characteristics for each 
drug. 
Other complications of the procedure: 
- 
- 
- 
- 
deterioration in general health 
decompensation of a chronic condition (diabetes, respiratory failure, etc.) 
cardiac decompensation 
acute confusion, disorientation 
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- 
- 
- 
- 
- 
- 
- 
- 
anaemia 
phlebitis/thrombophlebitis 
pulmonary embolism 
neurological complications (stroke, etc.) 
post-operative infections 
osteoarthritis 
bedsores 
malnutrition 
EvI of pathology under study: 
- 
- 
- 
- 
- 
- 
pain, 
loss of independence and immobilisation 
haematoma, blood loss-anaemia 
decompensation of general condition 
phlebitis 
pulmonary embolism and secondary cardiorespiratory or neurological complications 
AEs relating to possible ancillary treatments: expected AEs are listed in the SPC for medicines 
used within the scope of the MA or in the instructions for use for MDs used in accordance with the 
CE marking, therapeutic procedures implemented in accordance with recommendations and good 
professional practice 
6.3. 
MANAGEMENT OF ADVERSE EVENTS 
6.3.1. 
Collection of ADRs/AEs 
As part of this non-interventional research, the protocol does not involve any changes to the usual 
care of patients, so any adverse events or effects observed will be unrelated to the study. 
Under the investigator's responsibility, as with care, the reporting of complications from surgery 
(post-operative events), treatments, associated procedures or examinations is subject to regulated 
systems: ADRs related to medicines and medical devices are reported to pharmacovigilance and 
medical device vigilance systems, while complications from procedures and examinations are 
integrated into the risk management system of the establishments. 
As part of this study to assess the relationship between post-operative anaemia and independence, 
only complications that may have a potential impact on the study objective during hospitalisation and 
until the end of the study (i.e. 6 months post-operatively) will be collected and reported in the CRF: 
- 
Occurrence of a post-operative infection (pulmonary, urinary, surgical site, other) requiring 
antibiotic therapy. 
- 
- 
- 
Occurrence of acute urinary retention requiring urinary catheterisation 
Occurrence of prosthesis dislocation/loosening 
Iron deficiency (ferritin < 30 µg/L or CRP > 20 mg/L associated with a transferrin saturation 
coefficient < 15%) or vitamin deficiency (vitamin B12 < laboratory threshold and folate < 3.5 ng/mL) 
- 
- 
Record of transfusions and number of red blood cell concentrates administered. 
Occurrence of cardiovascular complications: deep vein thrombosis, pulmonary embolism, 
myocardial ischaemia (increased troponin) 
- 
Occurrence of neurological complications: stroke, cerebrovascular accident, etc. 
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- 
- 
- 
- 
- 
- 
Post-operative bleeding (including localised bleeding and gastrointestinal bleeding) 
Need for repeat surgery 
Occurrence of haematomas 
Recording of falls 
Records of fracture recurrence 
Need for re-hospitalisation (and reason) 
6.3.2. 
Notification of serious adverse events/serious adverse 
events requiring investigation 
SIs and AEs are reported to the appropriate vigilance channels (a copy will be kept in the patient's 
clinical file). 
Under this protocol, complications necessary for the analysis of the objective (see section 6.3.1) will 
be recorded in the CRF and analysed according to the study schedule (end of study). When there is 
a severity criterion in the context of an RNI, it is not necessary to notify the sponsor. 
Only new developments occurring during the research and any safety measures taken will be notified 
to the sponsor and reported to the competent authorities. 
6.3.3. 
Promoter notification period 
The investigator is responsible for collecting and reporting the various complications presented by 
patients to the appropriate vigilance system: 
- from inclusion 
- until the end of the study (M6) 
6.4. 
TERMS AND DURATION OF FOLLOW-UP OF PERSONS 
FOLLOWING THE OCCURRENCE OF ADVERSE EVENTS 
Any event, particularly a serious one, must be followed up until recovery, consolidation or death 
(closed event). 
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7. ADMINISTRATIVE AND REGULATORY ASPECTS 
7.1. 
RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS 
Each patient's medical data will only be disclosed to the sponsor or any person duly authorised by 
the sponsor and, where applicable, to the competent health authorities, under conditions that 
guarantee confidentiality. 
The sponsor and the supervisory authorities may request direct access to the medical file to verify 
the procedures and/or data of the clinical trial, within the limits authorised by laws and regulations. 
7.2. 
DATA CONFIDENTIALITY 
Persons with direct access shall take all necessary precautions to ensure the confidentiality of 
information relating to the persons involved, in particular with regard to their identity and the results 
obtained. 
These persons, like the investigators themselves, are subject to professional secrecy (under the 
conditions defined by Articles 226-13 and 226-14 of the Penal Code). 
During or at the end of the research, the data collected on the individuals involved and transmitted by 
the participants shall be anonymised. 
Under no circumstances shall the names or addresses of the persons concerned be disclosed. 
Only the first two letters of the subject's surname and the first letter of their first name will be 
recorded, accompanied by a coded number specific to the study indicating the order of inclusion of 
the subjects. 
7.3. 
COMPUTERISED DATA AND SUBMISSION TO THE CNIL 
The data collected as part of this study is collected for scientific research purposes, in the public 
interest. 
This study falls within the scope of the "Reference Methodology" MR-003 registered for the CHD 
Vendée under number 1995177 v 0 for the following reasons: 
- 
- 
- 
- 
- 
Collection of health data for research purposes 
Obtaining the opinion of a CPP to commence research 
Use of pseudo-anonymised data 
Individual information for the persons concerned 
Access to data only by professionals (healthcare and sponsor) involved in the study. 
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The fact that this study falls within the scope of MR003 and the reasons for this will be noted in the 
sponsor's processing register. 
7.4. 
MONITORING OF THE TRIAL 
Monitoring will be carried out by the internal promotion unit of the Clinical Research Unit. A Clinical 
Research Associate (CRA) will visit each investigator site regularly to perform quality control checks 
on the data reported in the observation logs. 
On-site monitoring visits will be organised after consultation with the investigator. CRAs must be able 
to consult the following at each site: 
- 
- 
- 
- 
the data collection notebooks for included patients, 
the patients' medical and nursing records, 
the investigator's file. 
7.5. 
INSPECTION/AUDIT 
An inspection or audit may be conducted as part of this study. The sponsor and/or participating 
centres must be able to provide inspectors or auditors with access to the data. 
7.6. 
ETHICAL CONSIDERATIONS 
7.6.1. 
Obtaining the patient's consent 
The investigator undertakes to obtain the non-objection of the patient/trusted person after providing 
them with information about the protocol (information note in the appendix). They will give them a 
copy of the information note. The person may only be included in the study after having read the 
information note and given their non-objection to participating in the study, after having had time to 
reflect, if necessary. 
The patient's information and consent to participate in the research must be noted in their medical 
records. 
7.6.2. 
Human Protection Committee 
The research manager undertakes to submit the study project for prior authorisation by a Human 
Protection Committee (CPP). The information provided covers 
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the methods and nature of the research and, secondly, the safeguards provided for patients 
participating in the trial. 
7.7. 
INFORMATION TO THE COMPETENT AUTHORITIES 
This protocol will be reported to the ANSM. 
7.8. 
AMENDMENTS TO THE PROTOCOL 
Requests for substantial amendments shall be submitted by the sponsor to the relevant CPP for its 
opinion in accordance with the law in force and its implementing decrees. 
The amended protocol must be updated and dated. 
The information form shall be amended if necessary. 
7.9. 
FUNDING 
The sponsor shall ensure the financing of the study. 
7.10. RULES RELATING TO PUBLICATION 
The study will be registered on a freely accessible website (Clinical Trial) before the first patient is 
included in the study. 
Scientific communications and reports relating to this study will be produced under the responsibility 
of the study coordinator with the agreement of the principal investigators of the participating centres. 
. 
Publication rules will follow international recommendations (N Engl J Med, 1997; 336:309-315). 
The first author must be a doctor from the Vendée Regional Hospital Centre: Romain DECOURS, 
geriatrician, Vendée Regional Hospital Centre. 
The second and penultimate authors will be Marine GEGU, geriatrician, CHD Vendée, and Ronan 
FEVRIER, geriatrician, CHD Vendée, respectively. 
The last author will be Laure de DECKER, geriatrician, Nantes University Hospital. 
The co-authors of the report and publications will be the investigators and clinicians involved, in 
proportion to their contribution to the study, as well as the biostatistician and associated researchers. 
A copy of the publication will be sent to the CHD Vendée, the study sponsor, which will necessarily 
be cited. 
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7.11. ARCHIVING OF SOURCE DATA 
The investigator must keep all information relating to the study for at least 15 years after the end of the 
study. 
At the end of the study, the investigator will receive a copy of the data for each patient from their 
centre, sent by the sponsor. 
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LIST OF APPENDICES 
❖ 
❖ 
❖ 
❖ 
Appendix 1 - Summary of the protocol 
Appendix 2 - Patient information sheet 
Appendix 3 – Information note for family/trusted person 
Appendix 4 – Scales and Scores 
❖ Appendix 5 – Data collection 
36