HemoDiafiltration Versus HemoDialysis in OLDER People: a Randomized, Multicenter, Crossover, Pragmatic Clinical Trial
Phase: NA
Conditions: Hemodialysis, Hemodiafiltration, Fatigue Symptom, Quality of Life of Patients, Older People
Sponsor: AUB Santé

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HD-Older 
Protocol full title: 
"HemoDiafiltration versus HemoDialysis in OLDER 
people: a randomized, multicenter, crossover, 
pragmatic clinical trial " 
Protocol short title/acronym: "HD-OLDER" 
Study Sponsor 
Name: Fondation AUB SANTE 
Address: 13 Boulevard de l'Odé, 35742 Pacé 
Telephone: 02 99 54 02 86 
Principal Investigator 
Name: Mabel AOUN 
Address: 68 Rue Labrouste, 75015, Paris, France 
Telephone: 07 49 70 28 28 
Email: aounmabel@yahoo.fr 
Co-investigators 
Thibault DOLLEY-HITZE1, Pablo URENA2, Guillaume SERET3, Simon 
DUQUENNOY1, Morgane GOSSELIN1, Eric LARUELLE1, Bruno LEGENDRE1, 
Rime OSSMANE2, Minh Hoang TRAN2, Wael EL HAGGAN3, Frédéric 
LAVAINNE3, Lurlings GENDROT3, Anne WUILLAI4  
Affiliations 
1AUB Santé, Bretagne, France 2AURA, Paris, France 3ECHO, France 4AIDER, France 

 
 
 
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Table of contents 
1. Study Synopsis ................................................................................ 
4  
2. Abbreviations ................................................................................. 
7 
 
3. Schedule of activities ...................................................................... 
8 
4. Background and Rationale .............................................................. 
9 
 
4.1. Background  
 
4.2. Risks and Benefits 
5. Study Objectives and Design ........................................................... 
10 
5.1. Study objectives 
5.2. Study Design 
5.3. Study Flowchart 
6. Selection and withdrawal of participants ........................................ 
11 
6.1. Selection of participants 
6.2. Inclusion criteria 
6.3. Exclusion criteria 
6.4. Permanent withdrawal of study 
6.5. Duration of trial 
7. Treatment of participants ............................................................... 
12 
8. Study phases .................................................................................. 
12 
9. Study procedures ........................................................................... 
13 
10. Study Outcomes ........................................................................... 
16 
9.1. Primary Endpoint 
9.2. Secondary Endpoints 
11. Assessment of safety ..................................................................... 
17 
12. Statistical methods ........................................................................ 
18 
12.1. Sample size 
12.2. Analysis 
 

 
 
 
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13. Study Organization ........................................................................ 
19 
13.1. Trial steering committee 
13.2. Scientific Advisory Board 
13.3. Independent data monitoring committee 
14. Recording of data- sources and electronic case report forms ......... 
19 
15. Data Quality Assurance ................................................................. 
20 
16. Data management ........................................................................ 
20 
17. Record retention ........................................................................... 
20 
18. Monitoring of the study ................................................................ 
21 
19. Data handling and confidentiality ................................................. 
20 
20. End of study, participant withdrawal and premature termination.... 20 
20.1. End of study and premature termination 
20.2. Participant withdrawal 
20.3. Participant replacement 
21. Deviations and violations ............................................................. 
22 
22. Ethical considerations, and Regulatory approvals ......................... 
22 
22.1. Regulatory authority/Ethics Committee 
22.2. Informed consent 
22.3. Amendments to protocol 
22.4. Dissemination of results 
22.5. Insurance 
22.6. Incentives 
23. References .................................................................................... 
25 
24. Questionnaires ............................................................................. 
26 
 
 
 

 
 
 
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1. Study Synopsis 
Title  
HemoDiafiltration versus HemoDialysis in OLDER 
people: a randomized, multicenter, crossover, 
pragmatic clinical trial 
Short title/Acronym 
HD-OLDER  
Study Phase  
Phase 4 
Sponsor Name 
AUB SANTE 
Principal Investigator 
Dr Mabel AOUN 
Data Protection Officer 
Mrs Mathilde COLLET (and Mrs Sibylle GOURVIL) 
ID-RCB (ANSM) 
2025-A00884-45 
Disease under investigation 
Stage 5 chronic kidney disease on Hemodialysis 
Study purpose 
To determine the best modality of hemodialysis in 
older patients > 84 years 
Study Design 
Randomized, multicenter, crossover, pragmatic 
clinical trial. 
Patients will be randomized to two sequences, each 
one of a 3-month period. Sequence 1 includes 3 
months of hemodiafiltration (Period 1) then 3 
months of high-flux hemodialysis (Period 2). 
Sequence 2 includes 3 months of high-flux 
hemodialysis (Period 1) then 3 months of 
hemodiafiltration (Period 2). 
Washout period 
Two weeks of low-flux hemodialysis at the 
beginning of the study and between the two periods 
of each sequence. 
Primary objective 
To compare the dialysis recovery time in older 
patients treated with hemodiafiltration versus 

 
 
 
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conventional high-flux hemodialysis 
Secondary objectives 
1.To compare the general fatigue between the two 
hemodialysis modalities 
2. To compare symptomatic hypotension and 
intradialytic clotting events 
3. To compare quality of life 
4. To compare dialysis adequacy  
5. To compare safety and adverse events 
Inclusion criteria 
A participant must meet ALL of the following criteria 
in order to participate: 
1-Signed and dated informed consent 
2-Age >84 years  
3-Diagnosed with kidney failure 
4-On maintenance hemodialysis>3 months 
5-Willing to have a dialysis session of 3.5 to 4-hour 
duration, three times a week 
6-Who has a reliable vascular access 
7-Who is covered by the health insurance 
Exclusion criteria 
A participant who meets one of the following 
criteria will be excluded: 
1-Patients with cognitive impairment (assessed with 
a mini-test if needed) 
2-Hospitalized at inclusion   
3-Who have difficulties with French speaking 
4-Terminally ill with life expectancy<3 months 
5-Active cancer 
Duration of study for each 
participant 
7 months (including 2 initial weeks of washout and 
2 weeks of washout between period 1 and period 2) 
Total duration of study 
8-10 months 
Primary Endpoint 
Change in dialysis recovery time (in minutes) 
between the start and end of period 1 and period 2. 
Secondary Endpoints 
-Change in fatigue score between the start and end 
of period 1 and period 2.  

 
 
 
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-Change in STS-30 between the start and end of 
period 1 and period 2. 
-Change in SF-12 scores between the start and end 
of period 1 and period 2. 
-Number of episodes of symptomatic hypotension 
in period 1 and period 2. 
-Number of intradialytic clotting events in period 1 
and period 2. 
-Change in hemoglobin, serum albumin, potassium, 
phosphate and Kt/V between the start and end of 
period 1 and period 2. 
-Secondary safety endpoints: serious adverse 
events (death, hospitalizations). 
Planned number of participants 
62 patients 
Statistical analysis 
Analyses will be performed on an intention-to-treat 
basis. Baseline characteristics will be compared 
using the independent t-test or Mann-Whitney U 
test for continuous variables and Chi-Square test for 
categorical variables. Linear mixed models will be 
used to compare the outcomes. 
Study Organization 
Trial steering committee  
Scientific Advisory Board  
Data and Safety Monitoring Board  
Ethics 
The study will be conducted according to the 
principles of the Declaration of Helsinki 1975 and 
will receive the approval of the ethics committee. 
Version 
and 
date 
of 
final 
protocol 
Version 1, 14/04/2025 
Version 3, 17/07/2025 
 

 
 
 
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2. Abbreviations 
 
HDF 
Hemodiafiltration 
HD 
Hemodialysis 
DRT 
Dialysis Recovery Time 
MCO 
Medium Cut-Off 
SNOSE 
Sequentially numbered opaque 
sealed envelope 
eCRF 
Electronic Case Report Form 
 
 
 
 
 
 
 
 
 
 

 
 
 
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3. Schedule of activities 
 
Washout 
Period 1 
Washout 
Period 2 
Visit 
Screening Randomi-
zation 
V1 
V2 
V3 
V4 
V5 
V6 
Week 
Day 0 or -
1 
Day 0 
2 weeks 
6 weeks 
6 weeks 
2 weeks 
6 weeks 
6 weeks 
Informed 
consent 
X 
 
 
 
 
 
 
 
Eligibility 
criteria 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Comorbidities 
and 
medications 
X 
 
 
 
 
 
 
 
Randomisation  
X 
 
 
 
 
 
 
Vital signs, 
weight 
X 
 
X 
X 
X 
X 
X 
X 
Vascular 
access 
X 
 
 
X 
 
 
X 
 
Routine 
Laboratory 
before and 
after dialysis§ 
X 
 
§ 
§ 
§ 
§ 
§ 
§ 
Concomitant 
medication 
X 
 
 
X 
 
 
X 
 
DRT question 
X 
 
X 
X 
X 
X 
X 
X 
Fatigue SONG-
questionnaire 
and STS-30 
X 
 
X 
X 
X 
X 
X 
X 
SF-12 Health 
Survey  
X 
 
 
 
X 
 
 
X 
Dialysis 
specifics* 
X 
 
X 
 
X 
X 
 
X 
Serious 
adverse events 
 
X 
X 
X 
X 
X 
X 
X 
§For routine laboratory tests, they will be done monthly during Period 1 (4 times) and 
Period 2 (4 times) *Symptomatic intradialytic hypotension and circuit clotting will be 
documented each session in medical charts and the total number entered in eCRF for 
Period 1 and for Period 2 

 
 
 
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4. Background and rationale 
4.1 Background 
 
Patients with kidney failure, treated with hemodialysis (HD) can be offered 
hemodiafiltration (HDF), high-flux hemodialysis (HD) or medium cut-off (MCO) 
hemodialysis. HD relies on the mechanism of diffusion to epurate toxins while HDF 
relies on diffusion and convection mechanisms, necessitating the use of high 
substitution fluid replacement, and may be more effective on middle molecules 
clearance. Before 2023, four studies compared the survival of patients treated with 
hemodiafiltration versus conventional hemodialysis. A meta-analysis of these studies 
showed a benefit of high-dose HDF therapy [1]. In 2023, the CONVINCE trial that 
included 1360 patients showed better survival in patients treated with post-dilution 
mode HDF at a dose > 23 liters in comparison to those treated with conventional high-
flux hemodialysis after a median follow-up of 30 months [2]. CONVINCE collected data 
on the quality of life and fatigue and showed a moderate positive effect for high-dose 
HDF on the cognitive function, without a significant difference on fatigue [3]. It is 
noteworthy that the mean age of patients included in the CONVINCE trial was 62.5 
years with no data on the older category of patients >84 years old.  
 
Dialysis recovery time has been used to assess post-dialysis fatigue and the 
tolerance of a dialysis session [4]. A randomized crossover clinical trial in 2017 
compared dialysis recovery time between patients on HDF and conventional high-flux 
HD, with a mean age of 65 years, and found no difference in recovery time between 
the two groups but they found more episodes of symptomatic hypotension and lower 
serum albumin on HDF [5]. A recent observational study of our research team on 
fatigue and recovery time found a significant association between HDF and prolonged 
dialysis recovery time in a sub-group of patients >84 years old [6]. This category of age 
was not addressed specifically in previous studies despite the aging of the kidney 
failure population. Thus, it is important to find out whether HDF is less or more 
beneficial than conventional HD in the very elderly population. 

 
 
 
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4.2. Risks and Benefits 
Risks 
HDF and High-Flux Conventional HD are two dialysis modalities routinely used in 
clinical practice in dialysis units. There is no increased risk related to both treatments. 
Benefits 
One of the two modalities may reduce the fatigue experienced by elderly dialysis 
patients during the post-dialysis period. 
 
5. Study Objectives and Design 
5.1. Study Objectives 
The primary objective is to compare the dialysis recovery time in patients treated with 
HDF versus those treated with conventional high-flux hemodialysis, after 3 months of 
therapy. The secondary objectives are to compare the general fatigue, health-related 
quality of life, symptomatic intradialytic hypotension, intradialytic circuit clotting, 
dialysis adequacy, safety and adverse events between the two dialysis modalities. 
5.2. Study design 
This is a randomized, multicenter, crossover, pragmatic clinical trial. Trial-group 
assignments will be performed using a computer generating algorithm. Patients will 
be assigned to one of two sequences: HD/HDF or HDF/HD. The allocation ratio is 1:1. 
Allocation concealment will be ensured using SNOSE (sequentially numbered opaque 
sealed envelope). This is a pragmatic trial: after randomization, physicians apply the 
best practice and keep the same membrane during the study. Healthcare provider and 
patient blinding is not possible because the HDF procedure cannot be hidden.  This 
study will assess the superiority of HDF over HD. This study will take place in 10 dialysis 
units in France. 

 
 
 
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5.3. Study flow chart 
 
 
 
 
 
 
 
 
 
 
 
 
6. Selection and withdrawal of patients  
6.1. Study setting and patient selection 
Hemodialysis patients will be recruited from 10 HD centers in France.  
6.2. Inclusion criteria 
All patients >84 years old, with chronic kidney disease stage 5, on maintenance 
hemodialysis for >3 months, willing to receive 3.5 to 4-hour sessions three times per 
week, with a reliable vascular access, who are covered by a health insurance and who 
sign an informed consent, will be included.  
6.3. Exclusion criteria 
Patients who are hospitalized at the moment of inclusion, with cognitive impairment 
(assessed with a mini-Cog test if needed), active cancer patients and participants who 
are terminally ill defined as having an expected survival of less than 3 months, and 
those who difficulties in French speaking, will be excluded.  
Patients >84 years old, undergoing 
hemodialysis for >3 months 
Randomization HD/HDF or HDF/HD (1:1) 
Period 1: 3 months of high-flux 
Period 1: 3 months of HDF 
2-week wash-out period 
2-week wash-out period 
2-week wash-out period 
2-week wash-out period 
Period 2: 3 months of HDF 
Period 2: 3 months of high-flux 

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6.4. Permanent withdrawal 
Participants have the right to withdraw from the study at any time for any reason. The 
investigator has also the right to withdraw patients from the study for medical reasons 
or in case of severe non-compliance. All patients who prematurely stopped should be 
followed for clinical events. 
6.5. Duration of trial 
Recruitment of patients will be done over 1-3 months or until the pre-determined 
sample size is reached whichever comes earlier. After randomization, the study for 
each participant has a duration of time of 7 months. 
7. Treatment of participants
Patients who are included will receive two weeks of low-flux hemodialysis then they 
will receive one of two sequences:  
Sequence 1 will receive HDF for three consecutive months (Period 1) then 
conventional high-flux HD for three consecutive months (Period 2).  
Sequence 2 will receive conventional high-flux HD for three consecutive months 
(Period 1) followed by HDF for three consecutive months (Period 2). 
Two weeks of washout with low-flux hemodialysis will be applied between the two 
periods (to ensure there will be no carry-over). 
8. Study phases
8.1. Screening
Patients who are eligible for the study will be verbally informed about the study. After 
being informed, each participant should sign and date the written informed consent 
form, approved by the ethics committee. A screening number will be allocated to each 
participant using the eCRF system.  

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8.2. Randomization 
Eligible participants will be randomized in a 1:1 ratio for HDF or high-flux 
hemodialysis using a centralized, web-based randomization module integrated into 
the electronic case report form (eCRF). Allocation concealment will be ensured 
because the treatment assignment will only be generated after the patient has been 
enrolled and all eligibility criteria have been confirmed within the eCRF system. 
Investigators and study personnel will not have access to the allocation sequence or 
block sizes prior to randomization.
8.3. Treatment phase 
Baseline is defined as the beginning of each period of three months. Data will 
be collected and study specific activities performed based on the Schedule of 
Activities.  
8.4. End of treatment 
All patients who complete the study will undergo an end of treatment visit. Any 
patient who prematurely withdraws is also to be followed for safety reasons and 
scheduled an end of treatment visit, unless the patient refuses. At a minimum, the 
investigator should make all efforts to obtain information on whether or not the 
participant is alive or dead at the end of study. 
9. Study procedures
All study activities, data collection and their timings are summarized in the Schedule 
of Activities. Baseline information about demographics, medical history, 
medications, dialysis prescription and laboratory results will be collected during 
routine clinical practice. All laboratory measurements will be conducted in the 
local laboratory of each dialysis unit. If laboratory results are not available, they 
should be recorded as non-available. 

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9.1. Data collection at screening/randomization 
Eligibility criteria: clearly stated and documented in the eCRF. 
Demographics: age, sex. 
Comorbidities and medical history: diabetes, smoking, hypertension, hyperlipidemia, 
cause and date of kidney failure (dialysis vintage), previous cardiovascular disease, 
atrial fibrillation, Charlson score for comorbidity.  
Vital signs: height and weight (dry weight). Pre-dialysis and post-dialysis systolic and 
diastolic blood pressure and heart rate in a sitting position will be recorded.  
Dialysis prescription: Vascular access (arteriovenous fistula or graft, central venous 
catheter); number of dialysis hours per week; dialysis session time (morning, 
afternoon, evening); blood flow, dialysate flow, dialysate temperature, filter 
membranes (surface), dialysate potassium, sodium, calcium content and type 
(acetate, HCL or citrate), anticoagulation type and dose (heparin or LMWH) will be 
collected. Use of UF control (or profile) or Na control (or profile).  
Laboratory pre-dialysis: urea, creatinine, serum phosphate, calcium, albumin, 
potassium, sodium, bicarbonate, hemoglobin, PTH, alkaline phosphatase, ferritin, 
transferrin saturation, uric acid, Kt/V (method of Kt/V assessment) to be recorded.  
Laboratory post-dialysis: urea, creatinine. 
Clinical variables: Urine volume will be assessed by collecting the 24 hour-urine and 
residual kidney function will be measured.  
Medications: antihypertensive therapy: number of drugs, diuretics, renin angiotensin 
aldosterone system inhibitors (RAASi), CCBs, beta-blockers, alpha-blockers; 
antidepressants and anxiolytics. Statin, medications for diabetes, oral anticoagulant, 
ESA, Iron, drugs for hyperkalemia, phosphate binders, vitamin D, cinacalcet. 

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Dialysis recovery time (DRT) will be collected for three consecutive sessions and will 
be assessed by asking "How long did it take you to recover from your last dialysis 
session?"[4] or in French "Combien de temps vous a-t-il fallu pour récupérer de votre 
dernière séance d'hémodialyse?". This question will be asked by nurses to each patient 
at each session for three consecutive sessions at the beginning, middle and end of 
each period of the trial. Answers were recorded in minutes or hours. 
Fatigue score will be assessed by using the French SONG-fatigue validated scale [7]. 
The SONG-HD fatigue scale includes three questions: in the last week, "did you feel 
tired?", "did you lack energy?", "did fatigue limit your usual activities?". The response 
to these questions follows a 4-Likert scale: 0= not at all, 1=a little, 2=quite a bit, 
3=severely. The total score of fatigue is defined as the sum of the three scores (0 to 
9).  
Stand-to-sit (STS 30) test: it is used to evaluate muscle performance and it is validated 
in patients on hemodialysis. It is assessed by asking the patient at the end of the 
session for three consecutive sessions to stand and sit on the chair as quickly as 
possible. The number of stand-to-sit over 30 seconds will be recorded. 
Health-related quality of life will be assessed using the SF-12 quality of life score. 
9.2. Data collection at follow-up 
Follow-up with laboratory measurements  
We will collect at baseline, one month, two months and three months of Period 1 and 
Period 2 the routine laboratory tests: serum urea, creatinine, phosphate, calcium, 
albumin, potassium, sodium, bicarbonate, hemoglobin, PTH, alkaline phosphatase, 
ferritin, transferrin saturation. 
At the end of each period, we will collect residual kidney function. 

 
 
 
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Clinical follow-up 
The number of symptomatic intradialytic hypotension episodes and of intradialytic 
clotting events will be documented in the patient’s chart at each session and the total 
number will be collected at the end of each period of treatment.  
Pre- and post-dialysis systolic and diastolic blood pressure will be collected at the end 
of each period of the trial by computing the average of the last three sessions. 
Number of hospital admissions and deaths, within each period, will be collected. 
Dialysis parameters follow-up 
We will collect at baseline, one month, two months and three months of each period 
of the trial: blood flow, dialysate flow, dialysate temperature, ultrafiltration rate 
(mL/Kg/h), Kt/V, convective volume (for HDF), use of UF control (or profile) or Na 
control (or profile), dialysis session duration and time (morning, afternoon, evening). 
Medications' follow-up 
Any change in baseline medications to be collected every month: antihypertensive 
therapy, ESA, Iron, drugs for hyperkalemia, phosphate binders, vitamin D, cinacalcet. 
Questionnaires 
DRT question, SONG-Fatigue questionnaire, STS-30 will be administered and recorded 
at baseline, 6 weeks and the end of Period 1 and Period 2.  
SF-12 Health Survey will be administered and recorded at baseline, and the end of 
Period 1 and Period 2. 
 
10. Study Outcomes 
10.1. Primary Endpoint 
-Change in dialysis recovery time (in minutes) between the start and end of period 1 
and period 2. 
 
 

 
 
 
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10.2. Secondary Endpoints 
-Change in fatigue score between the start and end of period 1 and period 2.  
-Change in STS-30 between the start and end of period 1 and period 2.  
-Change in SF-12 scores between between the start and end of period 1 and period 2. 
-Number of episodes of symptomatic hypotension in period 1 and period 2. 
-Number of intradialytic clotting events in period 1 and period 2. 
-Change in hemoglobin, serum albumin, potassium, phosphate and Kt/V between the 
start and end of period 1 and period 2. 
-Secondary safety endpoints: serious adverse events (death, hospitalizations). 
 
11. Assessment of safety 
11.1. Safety definitions 
Adverse event 
An adverse event is defined as an untoward, undesirable medical occurrence after 
exposure to a medical product, which is not necessarily caused by that medical 
product. 
Serious Adverse event 
A serious adverse event is suspected when the outcome of the event includes death, 
hospitalization, disability or permanent damage and required intervention to prevent 
permanent impairment or damage.  
Severity of adverse events 
Severity should be graded as mild, moderate, severe, life-threatening or leading to 
death.  
 
 

 
 
 
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11.2. Relatedness 
The relationship between an event and the study procedure should be assessed. Other 
possible causes of the event include: a worsening or change in manifestation of pre-
existing/underlying disease; progression of the treated disease; causal relationship 
with non-study treatment or other accident or intercurrent illness. 
 
11.3. Reporting of safety events 
This study compares two modalities of hemodialysis and related adverse events are 
very common in both treatment modalities, thus only serious adverse events will be 
reported. Serious adverse events and endpoints of these events will be recorded in 
the participant eCRF. Pre-existing conditions and pre-planned procedures prior to the 
patient's inclusion are not considered serious adverse events. Any serious adverse 
event should be reported to the sponsor within 24 hours of the investigator learning 
about the event. Given that death and non-fatal hospital admissions are common and 
normal part of the natural course of patients with end-stage kidney disease, all 
reported serious adverse events and deaths will be reported to regulatory authorities 
every 12 months using listings. 
 
12. Statistical methods 
12.1. Sample size  
Given that our previous study showed, in patients >84 years, a dialysis recovery time 
of 692 ± 741 minutes while using HDF and 423 ±646 minutes while using HD, if we 
consider a two-sided alpha of 5%, a power of 80%, the total sample size needed would 
be 56 patients. Assuming an attrition rate of 10%, we would need 62 patients.  
 The recruitment will go on until we reach this number. 
 

 
 
 
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12.2. Statistical analysis 
Continuous variables will be presented as mean ± standard deviation (SD) if they have 
normal distribution, otherwise as median and interquartile (IQR). Categorical variables 
will be reported as numbers and percentages. Differences between the study groups 
will be tested using χ2 tests (for categorical variables) and independent t test or Mann-
Whitney U test for continuous variables. Linear mixed models will be used to compare 
the outcomes in both periods of the trial. Analysis will be performed on an intention-
to-treat basis. Statistical analysis will be performed with SPSS. A P-value of ≤0.05 will 
be considered statistically significant. 
 
13. Study organization 
The trial steering committee is the highest decision-making body within the HD-
ELDERLY study. It consists of one representative of each participating dialysis unit and 
is chaired by the project coordinator. 
The Scientific Advisory Board will provide scientific advice concerning key project 
decisions and includes experts in hemodialysis from AUB SANTE. 
Data and Safety Monitoring Board is an independent committee that will ensure the 
safety of included patients is not compromised. 
 
14. Recording of data- sources and electronic case 
report forms  
This study data will be captured using an eCRF. Data will be collected from the 
patient's medical records, questionnaires administered during the study, laboratory 
reports, clinical and office charts, recorded data on dialysis generators. Every 
investigator and research staff of each dialysis unit will have access to the eCRF in 
order to enter data and make changes if needed.  

 
 
 
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Only authorized staff will have access to the eCRF. Data from the eCRF will be encoded 
and stored in a database at the sponsor site. An electronic data trail will capture all 
changes made to eCRF data, with date and time of change and reason for the 
modifications. Upon request from the sponsor, the investigators shall provide access 
to any background data in the medical records, especially in case of suspicion of data 
transcription error. Inspection or audits may also need access to the complete study 
records, provided that participant confidentiality is protected.  
15. Data Quality Assurance  
Every investigator is responsible for ensuring eCRF data are complete and accurate. 
The eCRF will be reviewed regularly by a monitor from the sponsor to ensure 
completeness and accuracy. They can also be reviewed by the sponsor's medical staff 
and corrections or clarifications would be necessary. Once a patient eCRF is complete, 
it will be locked (data will become read-only). Each investigator will provide an 
electronic signature of all eCRFs of their site before the data is analyzed.  
16. Data management 
The content of the eCRF will be created by the principal investigator and approved by 
the sponsor before the start of the study. All decisions concerning the eligibility 
criteria of participants will be done by the research staff at the sponsor site (after 
discussion with the principal investigator and the scientific advisory board if 
necessary) and any exclusion will be documented.  
17. Record retention 
Each investigator at each site must retain all study records for at least two years after 
the publication of the study or for a longer period depending on local regulatory 
requirements. Patient records and other source data must be kept for at least 15 
years. All records must be accessible to an audit or inspection. 
 

 
 
 
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18. Monitoring of the study, audits and inspections 
A research staff member designated by the sponsor will visit regularly each 
investigator to ensure that the study is progressing in accordance with the protocol 
and local regulations. During these visits, the research staff will be given access to all 
data related to the study.  
An audit may be also done at any time during or after completion of the study by the 
sponsor. A representative from local authorities can also inspect a study site and 
needs to have access to all data related to the study. The investigator of this site 
should contact the sponsor immediately if an inspection is taking place. 
19. Data handling and confidentiality 
Each investigator must assure that the participants anonymity will be maintained and 
their identities are protected from unauthorized parties. In eCRFs or other documents 
submitted to the sponsor, participants should not be identified by their names but by 
an identification code. The list of codes and names should be kept by each 
investigator. Participants written informed consents should be kept by each 
investigator, in strict confidence. 
20. End of study, participant withdrawal and premature 
termination 
20.1. End of study and premature termination 
The steering committee has the right to terminate the participation of either a 
participant or a site or the study at any time. Reasons for premature termination 
include: a high incidence of serious adverse events, the non-adherence of an 
investigator to the protocol or regulatory guidelines, unsatisfactory participant 
enrolment, inaccurate data recording or false information. 
 
 

 
 
 
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20.2. Participant withdrawal 
The reason for participant withdrawal should be recorded in the eCRF and includes 
one of the following: death, voluntary withdrawal, loss to follow-up, major protocol 
deviation, or study termination. 
Participants who are hospitalized will remain in the study. Participants continuing 
their treatment in a non-participating dialysis unit will be considered as dropped-out. 
They will be followed only for mortality. 
 
20.3. Participant replacement 
No participant can be replaced after randomization. 
 
21. Deviations and violations 
A deviation is an accidental or unintentional change to, or non-compliance with the 
study protocol and a violation is an accidental or unintentional change to, or non-
compliance with the ethics committee approved protocol without prior approval of 
the sponsor or the ethics committee. A deviation does not affect risks and benefits, 
does not have significant impact on participant's rights and safety. However, a 
violation generally increases risks and decreases benefits and affects the participant's 
rights and safety. All deviations and violations should be documented and followed up 
by the sponsor and reported to the regulatory authorities. 
 
22. Ethical considerations and Protection of human 
participants 
 

 
 
 
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22.1. Regulatory authority/Ethics committee 
The study will be conducted in agreement with the Helsinki Declaration of 1975 and 
the French laws and regulations. Approval from the ethics committee/CPP/IRB will be 
obtained before the study starts and will be communicated to each investigator. 
The trial will be registered on ClinicalTrials.gov. 
22.2. Informed consent 
Every participant will give his/her written informed consent (French version, attached 
to the protocol), in accordance with the Declaration of Helsinki and the European data 
protection regulation (Règlement Européen (UE) 2016/679 du 27 Avril 2016 relatif à 
la protection des données personnelles (RGPD) et la loi n° 78-17 du 06 Janvier 1978 
relative à l’informatique, aux fichiers et aux libertés modifiée et l'article L. 1121-1 du 
code de la santé publique).  
The principal investigator prepares the informed consent form and submits it to the 
ethics committee along with the protocol for approval.  
Before enrolling in the study, the investigator must provide potential participants 
and/or their legal representatives with an explanation of the study's objectives, 
methods, and potential benefits and risks. Participants will be informed that their 
involvement is voluntary and that they may withdraw consent at any time. They will 
also be assured that opting out will not affect the treatment they receive for their 
condition. Additionally, participants will be made aware that alternative treatments 
are available if they choose not to participate, and this decision will not affect their 
access to future treatments. Participants will be informed that a participant 
identification register will be maintained for potential long-term follow-up, and their 
medical records may be accessed by health authorities and authorized sponsor staff, 
in compliance with applicable laws and regulations, without compromising their 
confidentiality. By signing the informed consent form, participants authorize this 
access and consent to being contacted by their study physician for additional safety 
evaluations or to provide information about their vital status. 

 
 
 
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Participants will be given adequate time to read the informed consent form and have 
the opportunity to ask any questions. Once the explanation is provided and before 
entering the study, the participant’s consent must be properly documented with the 
participant’s personally dated signature and the investigator's personally dated 
signature. After obtaining consent, a copy of the informed consent form must be 
provided to the participant. 
If the participant is unable to read or write, an impartial witness must be present 
throughout the informed consent form process, including reading and explaining all 
written information. The witness must personally date and sign the form after 
obtaining oral consent from the participant. Copies of the signed form will be given to 
the participant, and the original will be kept in the participant's records. If new safety 
information leads to significant changes in the risk/benefit assessment, the form 
should be reviewed and updated if needed. All participants must be informed of any 
new information and provide their consent to continue with the study. 
22.3. Protocol amendments 
Protocol amendments will be communicated to the ethics committee. 
22.4. Dissemination of results 
Results will be disseminated to all investigators and regulatory authorities within 3 
months of the final analysis.  
22.5. Insurance 
The sponsor provides an insurance for participants during the period of the study, in 
accordance with the legal requirements. this insurance covers for damage to 
participants through injury or death caused by the study. 
22.6. Incentives 
No incentives will be given to participants. 
 
 

 
 
 
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23. References 
1. Peters SA, Bots ML, Canaud B, et al. Haemodiafiltration and mortality in end-stage 
kidney disease patients: a pooled individual participant data analysis from four 
randomized 
controlled 
trials. Nephrol 
Dial 
Transplant. 
2016;31(6):978-984. 
doi:10.1093/ndt/gfv349 
2. Blankestijn PJ, Vernooij RWM, Hockham C, et al. Effect of Hemodiafiltration or 
Hemodialysis on Mortality in Kidney Failure. N Engl J Med. 2023;389(8):700-709. 
doi:10.1056/NEJMoa2304820 
3. Rose M, Fischer FH, Liegl G, et al. The CONVINCE randomized trial found positive 
effects on quality of life for patients with chronic kidney disease treated with 
hemodiafiltration. Kidney Int. 2024;106(5):961-971. doi:10.1016/j.kint.2024.07.014 
4. Lindsay RM, Heidenheim PA, Nesrallah G, Garg AX, Suri R; Daily Hemodialysis Study 
Group London Health Sciences Centre. Minutes to recovery after a hemodialysis 
session: a simple health-related quality of life question that is reliable, valid, and 
sensitive to change. Clin J Am Soc Nephrol. 2006 Sep;1(5):952-9. doi: 
10.2215/CJN.00040106. Epub 2006 Jul 6. PMID: 17699312. 
5. Smith JR, Zimmer N, Bell E, Francq BG, McConnachie A, Mactier R. A Randomized, 
Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and 
Hemodiafiltration. Am 
J 
Kidney 
Dis. 
2017;69(6):762-770. 
doi:10.1053/j.ajkd.2016.10.025 
6. Aoun M, Laruelle E, Duneau G, et al. Modifiable Factors Associated with Prolonged 
Dialysis Recovery Time and Fatigue in Hemodialysis Patients. Kidney360. 
2024;5(9):1311-1321. doi:10.34067/KID.0000000000000532 
7. Mainguy A, Ju A, Tong A, et al. Validation de l’échelle SONG-Fatigue en Français. 
Néphrologie 
& 
Thérapeutique. 
2022;18(5):306-307.ISSN 
1769-7255. 
https://doi.org/10.1016/j.nephro.2022.07.235. 
 

 
 
 
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SF-12 questionnaire (French version) 
 
Questionnaire de qualité de vie liée à la santé: SF-12  
 
Les questions, qui suivent, portent sur votre état de santé telle que vous la ressentez. 
Ces informations nous permettront de mieux savoir comment vous vous sentez dans 
votre vie de tous les jours. Veuillez répondre à toutes les questions en entourant le 
chiffre correspondant à la réponse choisie, comme il est indiqué. Si vous ne savez pas 
très bien comment répondre, choisissez la réponse la plus proche dans votre situation.  
 
 
Dans l’ensemble, pensez-vous que votre santé est :  
1. Excellente 2. Très bonne 3. Bonne 4. Médiocre 5. Mauvaise  
 
 
Voici une liste d’activités que vous pouvez avoir à faire dans la vie de tous les jours. 
En raison de votre état de santé, êtes-vous limité(e) pour :  
• Des efforts physiques modérés (déplacer une table, passer l’aspirateur, jouer aux 
boules…) ?  
1. Oui, beaucoup limité(e) 2. Oui, un peu limité(e) 3. Non, pas du tout limité(e)  
 
• Monter plusieurs étages par l’escalier ?  
1. Oui, beaucoup limité(e) 2. Oui, un peu limité(e) 3. Non, pas du tout limité(e)  
 
 
 
Au cours de ces 4 dernières semaines, et en raison de votre état physique :  
• Avez-vous accompli moins de choses que vous auriez souhaité ?  
1. Oui 2. Non  
 
• Avez-vous dû arrêter certaines choses ?  
1. Oui 2. Non  
 
 
Au cours de ces 4 dernières semaines, et en raison de votre état émotionnel (comme 
vous sentir triste, nerveux(se) ou déprimé(e)) :  
• Avez-vous accompli moins de choses que vous auriez souhaité ?  
1. Oui 2. Non  
 
• Avez-vous eu des difficultés à faire ce que vous aviez à faire avec autant de soin 
et d’attention que d’habitude ?  
1. Oui 2. Non  
 
 
 
 
 
 
 
 
 
Tournez la page s’il vous plaît.  

 
 
 
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Au cours de ces 4 dernières semaines, dans quelle mesure vos douleurs physiques 
vous ont-elles limité(e) dans votre travail ou vos activités domestiques ?  
1. Pas du tout 2. Un petit peu 3. Moyennement 4. Beaucoup 5. Énormément  
 
 
Les questions qui suivent portent sur comment vous vous êtes senti(e) au cours de 
ces 4 dernières semaines. Pour chaque question, veuillez entourer la réponse qui vous 
semble la plus appropriée.  
• Y a-t-il eu des moments où vous vous êtes senti(e) calme et détendu(e) ?  
1. En permanence 2. Très souvent 3. Souvent 4. Quelques fois 5. Rarement 6. Jamais  
 
• Y a-t-il eu des moments où vous vous êtes senti(e) débordant(e) d’énergie ?  
1. En permanence 2. Très souvent 3. Souvent 4. Quelques fois 5. Rarement 6. Jamais  
 
• Y a-t-il eu des moments où vous vous êtes senti(e) triste et abattu(e) ?  
1. En permanence 2. Très souvent 3. Souvent 4. Quelques fois 5. Rarement 6. Jamais  
 
 
 
Au cours de ces 4 dernières semaines, y a-t-il eu des moments ou votre état de 
santé, physique ou émotionnel, vous a gêné(e) dans votre vie sociale et votre 
relation avec les autres, votre famille, vos amis, vos connaissances ?  
1. En permanence 2. Une bonne partie du temps 3. De temps en temps 4. Rarement 5. 
Jamais  
 
 
 
Veuillez vérifier que vous avez bien fourni une réponse pour chacune des questions.  
 
Merci d’avoir répondu au questionnaire.