Description

Study purpose: To determine the best modality of hemodialysis in older patients \> 84 years

Study Design: Randomized, multicenter, crossover, pragmatic clinical trial.

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 DATACAPT 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.

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.

Blinding: the participant, investigators and outcome assessors are not blinded the intervention.

Primary objective: To compare the dialysis recovery time in older patients treated with hemodiafiltration versus 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

Eligibility criteria: described under the section "Eligibility".

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

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.
• 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?" 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 will be recorded in minutes or hours.
• Fatigue score will be assessed by using the French SONG-fatigue validated scale. 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.

Data collection at follow-up

-Laboratory measurements The investigators will collect at 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, residual kidney function will be collected.

• 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 will be collected at 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 6 weeks and the end of Period 1 and Period 2. SF-12 Health Survey will be administered and recorded at the end of Period 1 and Period 2.

Primary and Secondary Endpoints: defined under the section "Outcome measures".

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.

Ethics: The study will be conducted according to the principles of the Declaration of Helsinki 1975.