Hemodialysis Adequacy Using a Heparin-grafted Dialyzer and a Citrate-enriched Dialysate

Study Overview
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Brief Summary
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After providing informed consent, patients will be randomized to either the intervention treatment (EvoCit procedure) or the control treatment (EvoHep procedure). After randomization, each study arm consists of four weeks of 3x4 hours hemodialysis treatments according to the allocated protocol. After the last dialysis treatment of the fourth treatment week and after a long interdialytic interval, patients will crossover to the alternative hemodialysis procedure. After crossover, the study will be completed with, again, four weeks of 3x4 hours hemodialysis treatments according to the allocated protocol.

Official Title
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Dialysis Adequacy and Clotting Complications During Anticoagulation-free Hemodialysis Using a Heparin-grafted Dialyzer and a Citrate-enriched Dialysate: a Prospective Randomized Crossover Study. (EvoCit-HD Study)

Conditions
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Kidney Diseases, Hemodialysis Complication, End Stage Renal Disease

Intervention / Treatment
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* Device: EvoCit
* Device: EvoHep


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated with hemodialysis or hemodiafiltration since at least three months. Hemodialysis or hemodiafiltration prescription of 3 x 4 hours weekly. ≥ 18 years of age. Patients able and agree to provide signed informed consent. Exclusion Criteria: Contraindication to heparin defined as known heparin-induced thrombopenia or active bleeding risk with contra-indication for systemic anticoagulation, categorized as defined by Swartz and Port1. Planned surgery during study period, including scheduled living-donor kidney transplantation during study period. Hypercoagulable state defined as known malignancy, known APC resistance/FV Leiden, known prothrombin gene mutation, known protein C or protein S deficiency, known antithrombin deficiency. Mean Qb of <300ml/min during one of the last 3 dialysis sessions before inclusion. 1 or more results of spKt/Vurea < 1,35 during the last three months prior to study inclusion. Need for 2 or more supplementary dialysis sessions on top of the regular 3x4 hours weekly hemodialysis regimen during the last month before inclusion. Vascular access dysfunction defined as use of urokinase the 2 months before study inclusion, including to restore catheter permeability. non-tunneled hemodialysis catheter use. known AV access outflow tract stenosis. planned vascular access intervention. planned vascular access conversion. Known allergy against heparin grafted AN69STmembranes. Use of ACE-inhibitor Use of vitamin K antagonist Use of novel oral anticoagulant therapy. Any medical condition, which puts the patient at risk of premature study termination in the opinion of the investigator. Planned conversion of dialysis modality during study period or planned absence/leave (including pregnancy or planned pregnancy). Symptomatic hypocalcemia. Hb < 8g/dl at screening. Hct > 45% at screening. Perdialytic total parenteral nutrition therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EvoCit<br>Standardized hemodialysis treatments 3x4hours/week. Intervention: EvoCit procedure using a heparin-grafted AN69ST dialyzer in combination with a citric acid enriched dialysate without any systemic anticoagulation. | Device: EvoCit<br>* hemodialysis using the combination of the Evodial dialyzer with a citrate enriched dialysate<br>|
| Active Comparator: EvoHep<br>Control: EvoHep procedure using a heparin-grafted AN69ST dialyzer in combination with a conventional bicarbonate-based dialysate and standardized systemic anticoagulation using unfractionated heparin. | Device: EvoHep<br>* hemodialysis using the combination of the Evodial dialyzer with a conventional bicarbonate based dialysate and systemic anticoagulation using unfractionated heparin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in dialysis adequacy | spKt/Vurea | every midweek dialysis session through study duration, ie 2x4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of thrombotic dysfunction | premature termination of the dialysis session | every HD session through study duration, ie 2x4 weeks | 
| change in dialysis adequacy expressed by middle molecule (MM) clearance | MM clearances | every 1st and 4th week HD session through study duration, ie 2x4 weeks | 
| occurence of complete circuit thrombosis | rapidly occurring thrombosis of the extracorporeal circuit, which does not allow complete retransfusion of the blood circuit even if prescribed treatment duration is reached | every HD session through study duration, ie 2x4 weeks | 
| change in membrane coagulation | total cell volume measurement of the dialyzer after hemodialysis | every midweek HD session through study duration, ie 2x4 weeks | 
| occurence of biological evaluation of coagulation activation | TAT, PF1+2, | every 1st and 4th week HD session through study duration, ie 2x4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dialysis adequacy, clotting