Hemodialysis Adequacy Using a Heparin-grafted Dialyzer and a Citrate-enriched Dialysate (EvoCit-HD)

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)

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.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; End Stage Renal Disease; Hemodialysis Complication
• Intervention / Treatment: Device: EvoCit; Device: EvoHep

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Jette, Belgium, 1090
    • UZ Brussel
  • Laeken, Belgium, 1020
    • CHU Brugmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

  1. use of urokinase the 2 months before study inclusion, including to restore catheter permeability.
  2. non-tunneled hemodialysis catheter use.
  3. known AV access outflow tract stenosis.
  4. planned vascular access intervention.
  5. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: "EvoCit"; 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; hemodialysis using the combination of the Evodial dialyzer with a citrate enriched dialysate
Active Comparator: "EvoHep"; 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; hemodialysis using the combination of the Evodial dialyzer with a conventional bicarbonate based dialysate and systemic anticoagulation using unfractionated heparin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Publications and helpful links

General Publications

• Francois K, De Clerck D, Tonnelier A, Cambier ML, Orlando C, Jochmans K, Cools W, Wissing KM. Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EvoCit Study. Am J Kidney Dis. 2022 Jan;79(1):79-87.e1. doi: 10.1053/j.ajkd.2021.04.004. Epub 2021 Apr 30.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Actual): December 4, 2019
• Study Completion (Actual): December 4, 2019

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 25, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 15, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: dialysis adequacy; clotting
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: UZB-NEF-2017-EvoCit-HD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No