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

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

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Device: EVODIAL dialyzer and Selectbag citrate; Device: Regional citrate anticoagulation

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 In several countries, UFH has gradually been replaced by low molecular weight heparins (LMWH).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
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patency of hemodialysis circuit	Completion of 4h dialysis session without circuit clotting that requires early treatment interruption	20 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Bjorn Meijers, MD, PhD, UZ Leuven

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 31, 2014
• First Posted (Estimate): November 2, 2014

Study Record Updates

• Last Update Posted (Estimate): May 13, 2016
• Last Update Submitted That Met QC Criteria: May 12, 2016
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Citric Acid; Sodium Citrate
• Other Study ID Numbers: S55895

Plan for Individual participant data (IPD)

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