CITrate and Evodial for Effective Dialysis (CITED) Study (CITED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02281045
Recruitment Status : Completed
First Posted : November 3, 2014
Last Update Posted : May 13, 2016
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:
It is not known whether the combination of a heparin-grafted membrane plus citrate-containing dialysate is a valid alternative to regional citrate anticoagulation. This is a cross-over non-inferiority trial comparing these two anticoagulation strategies

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Device: EVODIAL dialyzer and Selectbag citrate Device: Regional citrate anticoagulation Not Applicable

Detailed Description:

Anticoagulation is one of the supporting pillars of chronic hemodialysis (HD) (1). The optimal anticoagulant regimen provides full anticoagulation of the extracorporeal circuit with minimal systemic effects and comes at an affordable cost. Unfractionated heparin (UFH) has been the standard of care for many years. In several countries, UFH has gradually been replaced by low molecular weight heparins (LMWH). LMWH are easy to use as they can be administered as a bolus injection and reduce membrane fibrin and platelet deposition (2,1). Both UFH or LMWH provide adequate anticoagulation of the extracorporeal circuit, at the price of systemic anticoagulation. Apart from bleeding, the administration of unfractionated heparins has also been associated with dyslipidemia, hypoaldosteronism and hyperkalemia, thrombopenia, osteoporosis, pruritus, and hypersensitivity reactions.

Several alternative anticoagulation regimens have been proposed including heparin coating of the dialyzer membrane and regional citrate anticoagulation. Regional citrate anticoagulation is performed by infusing citrate into the arterial line of the dialysis tubing to reduce ionized calcium concentrations to very low levels (4,1). Ionized calcium concentrations are restored by calcium supplementation prior to reinfusion of the blood into the patient. Most often, calcium repletion is by calcium infusion into the venous line. Alternatively, a conventional calcium containing dialysate will restore calcium concentrations and, although the anticoagulant effect is blunted in the venous line, gives acceptable results (5). A previous study suggested that regional citrate anticoagulation is superior to heparin-coated polyacrylonitrile dialyzers (AN69ST; Nephral 300ST, Gambro) and resulted in in significantly greater instantaneous urea nitrogen clearances (3).

While generally safe and adequate, regional citrate anticoagulation requires additional actions during preparatory phase (preparation of citrate and calcium infusion pumps) as well as during the treatment (measurement of ionized calcium). These additional actions result in additional costs.

Recently, acetate-free citrate-containing dialysate concentrates were introduced into clinical practice. Besides the advantages of acetate-free dialysate, this provides a modest local anticoagulant effect inside the dialyzer. Citrate-containing dialysate allowed to reduce heparin dose while maintaining extracorporeal circuit patency and dialyzer clearances (6).

The investigators questioned whether combination of citrate-containing dialysate and heparin-coated dialyzer membranes is equally effective as conventional regional citrate anticoagulation.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CITrate and Evodial for Effective Dialysis (CITED) Study
Study Start Date : October 2014
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: EVODIAL dialyzer and Selectbag citrate
Intervention for anticoagulation during dialysis: Combination of Heparin-coated AN69ST membrane (EVODIAL, Gambro-Hospal, Meyzieu, France) and citrate-containing dialysate (Selectbag citrate, Gambro, Lund, Sweden).
Device: EVODIAL dialyzer and Selectbag citrate
Evodial is a trademark of Hospal-Gambro.

Active Comparator: Regional citrate anticoagulation
Regional citrate anticoagulation, using a hypertonic sterile solution of trisodium citrate dihydrate (1.035 Mol/L, Baxter, Lessines, Belgium), infused into the afferent blood line. Citrate will be infused at a rate of 62.1 mM/h (60 mL/h). The anticoagulant effect of citrate will be neutralized using calcium containing dialysate (Ca 1.50 mmol/L). Dialysate sodium content will be set at 135 mEQ/L, and bicarbonate will be reduced to 25 mEq/L.
Device: Regional citrate anticoagulation
Regional citrate anticoagulation is performed according to local practice, using a calcium-containing dialysate

Primary Outcome Measures :
  1. Patency of hemodialysis circuit [ Time Frame: 20 weeks ]
    Completion of 4h dialysis session without circuit clotting that requires early treatment interruption

Secondary Outcome Measures :
  1. Clotting of dialyser after the rinse [ Time Frame: 20 weeks ]
    scored semi-quantitatively on a visual scale (0: no clotting; 1: mild clotting; 2: severe clotting, 4: completely clotted).

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients aged over 18 years,
  • hemodynamic stability,
  • hemoglobin 9 - 12 g/dl.

Exclusion Criteria:

  • Any hemostatic disorder favoring either bleeding or clotting,
  • anti-vitamin K treatment,
  • risk of bleeding according to the criteria of Swartz (12).

Treatment with aspirin, dipyridamole or any drugs likely to interfere with platelet aggregation will be registered carefully, but will not be an exclusion criterion.

All vascular access types (AV-fistula, AV graft, catheter) are allowed. However, only patients with double route vascular access ('bipuncture') will be included in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02281045

Universitaire Ziekenhuizen Leuven
Leuven, Vlaams-Brabant, Belgium, 3000
University Hospitals Leuven
Leuven, Belgium, 3000
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Principal Investigator: Björn Meijers, MD, PhD UZ Leuven

Responsible Party: Universitaire Ziekenhuizen Leuven Identifier: NCT02281045     History of Changes
Other Study ID Numbers: S55895
First Posted: November 3, 2014    Key Record Dates
Last Update Posted: May 13, 2016
Last Verified: October 2014
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Citric Acid
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action